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Reward processing dysfunctions are considered a candidate mechanism underlying anhedonia and apathy in depression. Neuroimaging studies have documented that neurofunctional alterations in mesocorticolimbic circuits may neurally mediate these dysfunctions. However, common and distinct neurofunctional alterations during motivational and hedonic evaluation of monetary and natural rewards in depression have not been systematically examined. Here, we capitalized on pre-registered neuroimaging meta-analyses to (1) establish general reward-related neural alterations in depression, (2) determine common and distinct alterations during the receipt and anticipation of monetary v. natural rewards, and, (3) characterize the differences on the behavioral, network, and molecular level. The pre-registered meta-analysis (https://osf.io/ay3r9) included 633 depressed patients and 644 healthy controls and revealed generally decreased subgenual anterior cingulate cortex and striatal reactivity toward rewards in depression. Subsequent comparative analyses indicated that monetary rewards led to decreased hedonic reactivity in the right ventral caudate while natural rewards led to decreased reactivity in the bilateral putamen in depressed individuals. These regions exhibited distinguishable profiles on the behavioral, network, and molecular level. Further analyses demonstrated that the right thalamus and left putamen showed decreased activation during the anticipation of monetary reward. The present results indicate that distinguishable neurofunctional alterations may neurally mediate reward-processing alterations in depression, in particular, with respect to monetary and natural rewards. Given that natural rewards prevail in everyday life, our findings suggest that reward-type specific interventions are warranted and challenge the generalizability of experimental tasks employing monetary incentives to capture reward dysregulations in everyday life.
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Depressão , Motivação , Humanos , Depressão/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Neuroimagem , Recompensa , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologiaRESUMO
BACKGROUND AND PURPOSE: Thalamic alterations have been reported as a major feature in presymptomatic and symptomatic patients carrying the C9orf72 mutation across the frontotemporal dementia-amyotrophic lateral sclerosis (ALS) spectrum. Specifically, the pulvinar, a high-order thalamic nucleus and timekeeper for large-scale cortical networks, has been hypothesized to be involved in C9orf72-related neurodegenerative diseases. We investigated whether pulvinar volume can be useful for differential diagnosis in ALS C9orf72 mutation carriers and noncarriers and how underlying functional connectivity changes affect this region. METHODS: We studied 19 ALS C9orf72 mutation carriers (ALSC9+) accurately matched with wild-type ALS (ALSC9-) and ALS mimic (ALSmimic) patients using structural and resting-state functional magnetic resonance imaging data. Pulvinar volume was computed using automatic segmentation. Seed-to-voxel functional connectivity analyses were performed using seeds from a pulvinar functional parcellation. RESULTS: Pulvinar structural integrity had high discriminative values for ALSC9+ patients compared to ALSmimic (area under the curve [AUC] = 0.86) and ALSC9- (AUC = 0.77) patients, yielding a volume cutpoint of approximately 0.23%. Compared to ALSmimic, ALSC9- showed increased anterior, inferior, and lateral pulvinar connections with bilateral occipital-temporal-parietal regions, whereas ALSC9+ showed no differences. ALSC9+ patients when compared to ALSC9- patients showed reduced pulvinar-occipital connectivity for anterior and inferior pulvinar seeds. CONCLUSIONS: Pulvinar volume could be a differential biomarker closely related to the C9orf72 mutation. A pulvinar-cortical circuit dysfunction might play a critical role in disease progression and development, in both the genetic phenotype and ALS wild-type patients.
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Esclerose Lateral Amiotrófica , Proteína C9orf72 , Imageamento por Ressonância Magnética , Mutação , Pulvinar , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/diagnóstico por imagem , Esclerose Lateral Amiotrófica/fisiopatologia , Esclerose Lateral Amiotrófica/patologia , Proteína C9orf72/genética , Demência Frontotemporal/genética , Demência Frontotemporal/fisiopatologia , Demência Frontotemporal/diagnóstico por imagem , Demência Frontotemporal/patologia , Heterozigoto , Pulvinar/diagnóstico por imagem , Pulvinar/fisiopatologia , Pulvinar/patologiaRESUMO
Background: Maternal phenylketonuria (mPKU) is a pathologic condition occurring in the fetus of a mother with PKU that is caused by prolonged elevated intrauterine blood phenylalanine (Phe) levels, which can lead to congenital abnormalities and mental retardation of newborns. Management of PKU during pregnancy can be challenging as protein substitutes may exacerbate nausea, vomiting, and gastrointestinal symptoms. Aim: To report the successful management of four PKU pregnant women. Methods: The patients were administered with prolonged-release amino acid supplementation and were recommended to follow a strict diet. Blood Phe concentration, adherence to diet, and occurrence of adverse events were monitored. Results: All patients achieved safe levels of blood Phe concentration (120-360 µmol/L) since preconception and during pregnancy (mean Phe concentration values of 143.34 ± 137.59, 226.48 ± 194.57, 186.68 ± 133.67, and 187.47 ± 42.59 µmol/L). During the first trimester of pregnancy, all patients manifested gastrointestinal symptoms such as nausea, gastrointestinal reflux, and abdominal bloating, which were managed by either changing protein substitute or extending the time window between different meals and amino acid mixtures administration. The four women continued their pregnancies without experiencing further complications and delivered neonates with normal growth parameters and no malformations. Conclusion: Findings of this case series suggest that the intake of a prolonged-release amino acid mixture in granules is well tolerated by pregnant PKU patients, eventually leading to good metabolic control and fetal growth within normal ranges.
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BACKGROUND: Despite hypothalamus has long being considered to be involved in the pathophysiology of cluster headache, the inconsistencies of previous neuroimaging studies and a limited understanding of the hypothalamic areas involved, impede a comprehensive interpretation of its involvement in this condition. METHODS: We used an automated algorithm to extract hypothalamic subunit volumes from 105 cluster headache patients (57 chronic and 48 episodic) and 59 healthy individuals; after correcting the measures for the respective intracranial volumes, we performed the relevant comparisons employing logist regression models. Only for subunits that emerged as abnormal, we calculated their correlation with the years of illness and the number of headache attacks per day, and the effects of lithium treatment. As a post-hoc approach, using the 7 T resting-state fMRI dataset from the Human Connectome Project, we investigated whether the observed abnormal subunit, comprising the paraventricular nucleus and preoptic area, shows robust functional connectivity with the mesocorticolimbic system, which is known to be modulated by oxytocin neurons in the paraventricular nucleus and that is is abnormal in chronic cluster headache patients. RESULTS: Patients with chronic (but not episodic) cluster headache, compared to control participants, present an increased volume of the anterior-superior hypothalamic subunit ipsilateral to the pain, which, remarkably, also correlates significantly with the number of daily attacks. The post-hoc approach showed that this hypothalamic area presents robust functional connectivity with the mesocorticolimbic system under physiological conditions. No evidence of the effects of lithium treatment on this abnormal subunit was found. CONCLUSIONS: We identified the ipsilateral-to-the-pain antero-superior subunit, where the paraventricular nucleus and preoptic area are located, as the key hypothalamic region of the pathophysiology of chronic cluster headache. The significant correlation between the volume of this area and the number of daily attacks crucially reinforces this interpretation. The well-known roles of the paraventricular nucleus in coordinating autonomic and neuroendocrine flow in stress adaptation and modulation of trigeminovascular mechanisms offer important insights into the understanding of the pathophysiology of cluster headache.
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Cefaleia Histamínica , Humanos , Cefaleia Histamínica/terapia , Dor , Cefaleia , Hipotálamo/diagnóstico por imagem , Compostos de LítioRESUMO
BACKGROUND: Mindfulness practice has gained interest in the management of Chronic Migraine associated with Medication Overuse Headache (CM-MOH). Mindfulness is characterized by present-moment self-awareness and relies on attention control and emotion regulation, improving headache-related pain management. Mindfulness modulates the Default Mode Network (DMN), Salience Network (SN), and Fronto-Parietal Network (FPN) functional connectivity. However, the neural mechanisms underlying headache-related pain management with mindfulness are still unclear. In this study, we tested neurofunctional changes after mindfulness practice added to pharmacological treatment as usual in CM-MOH patients. METHODS: The present study is a longitudinal phase-III single-blind Randomized Controlled Trial (MIND-CM study; NCT03671681). Patients had a diagnosis of CM-MOH, no history of neurological and severe psychiatric comorbidities, and were attending our specialty headache centre. Patients were divided in Treatment as Usual (TaU) and mindfulness added to TaU (TaU + MIND) groups. Patients underwent a neuroimaging and clinical assessment before the treatment and after one year. Longitudinal comparisons of DMN, SN, and FPN connectivity were performed between groups and correlated with clinical changes. Vertex-wise analysis was performed to assess cortical thickness changes. RESULTS: 177 CM-MOH patients were randomized to either TaU group or TaU + MIND group. Thirty-four patients, divided in 17 TaU and 17 TaU + MIND, completed the neuroimaging follow-up. At the follow-up, both groups showed an improvement in most clinical variables, whereas only TaU + MIND patients showed a significant headache frequency reduction (p = 0.028). After one year, TaU + MIND patients showed greater SN functional connectivity with the left posterior insula (p-FWE = 0.007) and sensorimotor cortex (p-FWE = 0.026). In TaU + MIND patients only, greater SN-insular connectivity was associated with improved depression scores (r = -0.51, p = 0.038). A longitudinal increase in cortical thickness was observed in the insular cluster in these patients (p = 0.015). Increased anterior cingulate cortex thickness was also reported in TaU + MIND group (p-FWE = 0.02). CONCLUSIONS: Increased SN-insular connectivity might modulate chronic pain perception and the management of negative emotions. Enhanced SN-sensorimotor connectivity could reflect improved body-awareness of painful sensations. Expanded cingulate cortex thickness might sustain improved cognitive processing of nociceptive information. Our findings unveil the therapeutic potential of mindfulness and the underlying neural mechanisms in CM-MOH patients. TRIAL REGISTRATION: Name of Registry; MIND-CM study; Registration Number ClinicalTrials.gov identifier: NCT0367168; Registration Date: 14/09/2018.
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Transtornos da Cefaleia Secundários , Atenção Plena , Humanos , Atenção Plena/métodos , Transtornos da Cefaleia Secundários/terapia , Transtornos da Cefaleia Secundários/psicologia , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Estudos Longitudinais , Método Simples-Cego , Imageamento por Ressonância Magnética , Rede de Modo Padrão/diagnóstico por imagem , Rede de Modo Padrão/fisiopatologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/fisiopatologiaRESUMO
Neurobiological pain models propose that chronic pain is accompanied by neurofunctional changes that mediate pain processing dysfunctions. In contrast, meta-analyses of neuroimaging studies in chronic pain conditions have not revealed convergent evidence for robust alterations during experimental pain induction. Against this background, the present neuroimaging meta-analysis combined three different meta-analytic approaches with stringent study selection criteria for case-control functional magnetic resonance imaging experiments during acute pain processing with a focus on chronic pain disorders. Convergent neurofunctional dysregulations in chronic pain patients were observed in the left anterior insula cortex. Seed-based resting-state functional connectivity based on a large publicly available dataset combined with a meta-analytic task-based approach identified the anterior insular region as a key node of an extended bilateral insula-fronto-cingular network, resembling the salience network. Moreover, the meta-analytic decoding showed that this region presents a high probability to be specifically activated during pain-related processes, although we cannot exclude an involvement in autonomic processes. Together, the present findings indicate that dysregulated left anterior insular activity represents a robust neurofunctional maladaptation and potential treatment target in chronic pain disorders.
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Dor Crônica/diagnóstico por imagem , Dor Crônica/fisiopatologia , Neuroimagem Funcional , Córtex Insular/diagnóstico por imagem , Córtex Insular/fisiopatologia , HumanosRESUMO
BACKGROUND: Despite a growing understanding of disorders of consciousness following severe brain injury, the association between long-term impairment of consciousness, spontaneous brain oscillations, and underlying subcortical damage, and the ability of such information to aid patient diagnosis, remains incomplete. METHODS: Cross-sectional observational sample of 116 patients with a disorder of consciousness secondary to brain injury, collected prospectively at a tertiary center between 2011 and 2013. Multimodal analyses relating clinical measures of impairment, electroencephalographic measures of spontaneous brain activity, and magnetic resonance imaging data of subcortical atrophy were conducted in 2018. RESULTS: In the final analyzed sample of 61 patients, systematic associations were found between electroencephalographic power spectra and subcortical damage. Specifically, the ratio of beta-to-delta relative power was negatively associated with greater atrophy in regions of the bilateral thalamus and globus pallidus (both left > right) previously shown to be preferentially atrophied in chronic disorders of consciousness. Power spectrum total density was also negatively associated with widespread atrophy in regions of the left globus pallidus, right caudate, and in the brainstem. Furthermore, we showed that the combination of demographics, encephalographic, and imaging data in an analytic framework can be employed to aid behavioral diagnosis. CONCLUSIONS: These results ground, for the first time, electroencephalographic presentation detected with routine clinical techniques in the underlying brain pathology of disorders of consciousness and demonstrate how multimodal combination of clinical, electroencephalographic, and imaging data can be employed in potentially mitigating the high rates of misdiagnosis typical of this patient cohort.
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Lesões Encefálicas , Estado de Consciência , Atrofia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Lesões Encefálicas/patologia , Estudos Transversais , Eletroencefalografia , Humanos , Imageamento por Ressonância Magnética/métodosRESUMO
Spinocerebellar ataxias type 1 (SCA1) is an autosomal dominant disease usually manifesting in adulthood. We performed a prospective 1-year longitudinal study in 14 presymptomatic mutation carriers (preSCA1), 11 ataxic patients, and 21 healthy controls. SCA1 patients had a median disease duration of 6 years (range 2-16) and SARA score of 7 points (range 3.5-20). PreSCA1 had an estimated time before disease onset of 9.7 years (range 4-30), and no signs of ataxia. At baseline, SCA1 patients significantly differed from controls in SARA score (Scale for Assessment and Rating of Ataxia), cognitive tests, and structural MRI measures. Significant volume loss was found in cerebellum, brainstem, basal ganglia, and cortical thinning in frontal, temporal, and occipital regions. PreSCA1 did not differ from controls. At 1-year follow-up, SCA1 patients showed significant increase in SARA score, and decreased volume of cerebellum (- 0.6%), pons (- 5.5%), superior cerebellar peduncles (- 10.7%), and midbrain (- 3.0%). Signs of disease progression were also observed in preSCA1 subjects, with increased SARA score and reduced total cerebellar volume. Our exploratory study suggests that clinical scores and MRI measures provide valuable data to monitor and quantify the earliest changes associated with the preclinical and the symptomatic phases of SCA1 disease.
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Ataxias Espinocerebelares , Adulto , Progressão da Doença , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Estudos Prospectivos , Ataxias Espinocerebelares/complicações , Ataxias Espinocerebelares/diagnóstico por imagem , Ataxias Espinocerebelares/genéticaRESUMO
PURPOSE: Previous studies on brain morphological alterations in chronic cluster headache revealed inconsistent findings. METHOD: The present cross-sectional explorative study determined telencephalic and cerebellar cortex thickness alterations in a relatively wide sample of chronic cluster headache patients (n = 28) comparing them to matched healthy individuals. RESULTS: The combination of two highly robust state-of-the-art approaches for thickness estimation (Freesurfer, CERES), strengthened by functional characterization of the identified abnormal regions, revealed four main results: chronic cluster headache patients show 1) cortical thinning in the right middle cingulate cortex, left posterior insula, and anterior cerebellar lobe, regions involved in nociception's sensory and sensory-motor aspects and possibly in autonomic functions; 2) cortical thinning in the left anterior superior temporal sulcus and the left collateral/lingual sulcus, suggesting neuroplastic maladaptation in areas possibly involved in social cognition, which may promote psychiatric comorbidity; 3) abnormal functional connectivity among some of these identified telencephalic areas; 4) the identified telencephalic areas of cortical thinning present robust interaction, as indicated by the functional connectivity results, with the left posterior insula possibly playing a pivotal role. CONCLUSION: The reported results constitute a coherent and robust picture of the chronic cluster headache brain. Our study paves the way for hypothesis-driven studies that might impact our understanding of the pathophysiology of this condition.
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Cefaleia Histamínica , Córtex Cerebelar , Afinamento Cortical Cerebral , Cefaleia Histamínica/diagnóstico por imagem , Estudos Transversais , Humanos , Imageamento por Ressonância Magnética/métodosRESUMO
BACKGROUND: Converging evidence suggests that anatomical and functional mesocorticolimbic abnormalities support the chronicization of pain disorders. METHODS: We mapped structural and functional alterations of the mesocorticolimbic system in a sample of chronic cluster headache patients (n = 28) in comparison to age and sex-matched healthy individuals (n = 28) employing structural MRI and resting-state functional MRI. RESULTS: Univariate logistic regression models showed that several of the examined structures/areas (i.e., the bilateral nucleus accumbens, ventral diencephalon, hippocampus, and frontal pole, and the right amygdala) differentiated chronic cluster headache patients from healthy individuals (p < 0.05, uncorrected). Specifically, all the significant structures/areas had increased volumes in chronic cluster headache patients compared to healthy individuals. The examination of the groups suffering from left and right-sided cranial attacks showed a lateralization effect: ipsilateral to the pain ventral diencephalic regions and contralateral to the pain nucleus accumbens discriminated chronic cluster headache patients from healthy individuals. The resting-state functional MRI data analyses showed that chronic cluster headache patients compared to CTRL individuals present robust reduced functional connectivity in the right frontal pole-right amygdala pathway (p < 0.05, FDR-corrected). CONCLUSION: Our results showed that chronic cluster headache patients present anatomical and functional maladaptation of the mesocorticolimbic system, with functional data indicating a possible prefrontal areas' failure to modulate the mesolimbic structures. These results were opposite to what we hypothesized based on the previous literature on chronic pain conditions.Future studies should assess whether the observed mesocorticolimbic abnormalities are due to the neuroprotective effects of the assumed medications, or to the frequent comorbidity of CH with neuropsychiatric disorders or if they are a genuine neural signature of CH and/or chronic cluster headache condition.
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Cefaleia Histamínica , Transtornos da Cefaleia , Tonsila do Cerebelo/diagnóstico por imagem , Encéfalo , Cefaleia Histamínica/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Vias Neurais/diagnóstico por imagem , DorRESUMO
If conceptual retrieval is partially based on the simulation of sensorimotor experience, people with a different sensorimotor experience, such as congenitally blind people, should retrieve concepts in a different way. However, studies investigating the neural basis of several conceptual domains (e.g., actions, objects, places) have shown a very limited impact of early visual deprivation. We approached this problem by investigating brain regions that encode the perceptual similarity of action and color concepts evoked by spoken words in sighted and congenitally blind people. At first, and in line with previous findings, a contrast between action and color concepts (independently of their perceptual similarity) revealed similar activations in sighted and blind people for action concepts and partially different activations for color concepts, but outside visual areas. On the other hand, adaptation analyses based on subjective ratings of perceptual similarity showed compelling differences across groups. Perceptually similar colors and actions induced adaptation in the posterior occipital cortex of sighted people only, overlapping with regions known to represent low-level visual features of those perceptual domains. Early-blind people instead showed a stronger adaptation for perceptually similar concepts in temporal regions, arguably indexing higher reliance on a lexical-semantic code to represent perceptual knowledge. Overall, our results show that visual deprivation does changes the neural bases of conceptual retrieval, but mostly at specific levels of representation supporting perceptual similarity discrimination, reconciling apparently contrasting findings in the field.
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Adaptação Fisiológica/fisiologia , Cegueira/fisiopatologia , Mapeamento Encefálico , Cor , Formação de Conceito/fisiologia , Rememoração Mental/fisiologia , Lobo Occipital/fisiologia , Percepção da Fala/fisiologia , Lobo Temporal/fisiologia , Adulto , Cegueira/congênito , Percepção de Cores/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-IdadeRESUMO
One of the major challenges for clinicians who treat patients with Disorders of Consciousness (DoCs) concerns the detection of signs of consciousness that distinguish patients in Vegetative State from those in Minimally Conscious State. Recent studies showed how visual responses to tailored stimuli are one of the first evidence revealing that one patient is changing from one state to another. This study aimed to explore the integrity of the neural structures being part of the visual system in patients with DoCs manifesting a reflexive behavior (visual blink) and in those manifesting a cognitively and cortically mediated behavior (visual pursuit). We collected instrumental data using specialized equipment (EEG following the rules of the International 10-20 system, 3T Magnetic Resonance, and Positron Emission Tomography) in 54 DoC patients. Our results indicated that visual pursuit group showed a better fVEPs response than the visual blink group, because of a greater area under the N2/P2 component of fVEPs (AUC could be seen as an indicator of the residual activity of visual areas). Considering neuroimaging data, the main structural differences between groups were found in the retrochiasmatic areas, specifically in the right optic radiation and visual cortex (V1), areas statistically less impaired in patients able to perform a visual pursuit. FDG-PET analysis confirmed difference between groups at the level of the right calcarine cortex and neighboring right lingual gyrus. In conclusion, although there are methodological and theoretical limitations that should be considered, our study suggests a new perspective to consider for a future diagnostic protocol.
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Estado de Consciência , Estado Vegetativo Persistente , Humanos , Imageamento por Ressonância Magnética , Neuroimagem , Tomografia por Emissão de Pósitrons , Percepção VisualRESUMO
The comprehension of cluster headache (CH) has greatly benefited from the tremendous progress of the neuroimaging techniques over the last 20 years. Since the pioneering study of May et al. (1998), the neuroimaging results have indeed revolutionized the conception of this disease, now considered as a dysfunction of the central nervous system. Clinical, neuroendocrinological, and neuroimaging studies strongly suggested the involvement of the hypothalamus as the generator of cluster headache attacks. However, the latency of the improvement and the inefficacy of the hypothalamic deep brain stimulation (DBS) in the acute phase suggested that the hypothalamus might play a modulating role, pointing to the presence of some dysfunctional brain networks, normalized or modulated by the DBS. Despite the great importance of possible dysfunctional hypothalamic networks in cluster headache pathophysiology, only quite recently the scientific community has begun to explore the functional connectivity of these circuits using resting-state functional magnetic resonance imaging. This is a neuroimaging technique extensively employed to investigate the functional connectivity among separated regions of the brain at rest in the low-frequency domain (< 0.1 Hz). Here, we present a review of the few resting-state functional magnetic resonance imaging studies investigating the hypothalamic network contributing to a deeper comprehension of this neurological disorder. These studies seem to demonstrate that both the hypothalamus and the diencephalic-mesencephalic junction regions might play an important role in the pathophysiology of CH. However, future studies are needed to confirm the results and to clarify if the observed dysfunctional networks are a specific neural fingerprint of the CH pathophysiology or an effect of the severe acute pain. It will be also crucial to clarify the neural pathways of the chronicization of this disorder.
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Encéfalo/diagnóstico por imagem , Cefaleia Histamínica/fisiopatologia , Vias Neurais/fisiopatologia , Neuroimagem , Cefaleia Histamínica/diagnóstico por imagem , Estimulação Encefálica Profunda/métodos , Humanos , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodosRESUMO
OBJECTIVE: We tested the hypothesis of a defective functional connectivity between the posterior hypothalamus and diencephalic-mesencephalic regions in chronic cluster headache based on: a) clinical and neuro-endocrinological findings in cluster headache patients; b) neuroimaging findings during cluster headache attacks; c) neuroimaging findings in drug-refractory chronic cluster headache patients improved after successful deep brain stimulation. METHODS: Resting state functional magnetic resonance imaging, associated with a seed-based approach, was employed to investigate the functional connectivity of the posterior hypothalamus in chronic cluster headache patients (n = 17) compared to age and sex-matched healthy subjects (n = 16). Random-effect analyses were performed to study differences between patients and controls in ipsilateral and contralateral-to-the-pain posterior hypothalamus functional connectivity. RESULTS: Cluster headache patients showed an increased functional connectivity between the ipsilateral posterior hypothalamus and a number of diencephalic-mesencephalic structures, comprising ventral tegmental area, dorsal nuclei of raphe, and bilateral substantia nigra, sub-thalamic nucleus, and red nucleus ( p < 0.005 FDR-corrected vs . control group). No difference between patients and controls was found comparing the contralateral hypothalami. CONCLUSIONS: The observed deranged functional connectivity between the posterior ipsilateral hypothalamus and diencephalic-mesencephalic regions in chronic cluster headache patients mainly involves structures that are part of (i.e. ventral tegmental area, substantia nigra) or modulate (dorsal nuclei of raphe, sub-thalamic nucleus) the midbrain dopaminergic systems. The midbrain dopaminergic systems could play a role in cluster headache pathophysiology and in particular in the chronicization process. Future studies are needed to better clarify if this finding is specific to cluster headache or if it represents an unspecific response to chronic pain.
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Encéfalo/fisiopatologia , Cefaleia Histamínica/fisiopatologia , Vias Neurais/fisiopatologia , Adulto , Encéfalo/diagnóstico por imagem , Cefaleia Histamínica/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Vias Neurais/diagnóstico por imagemRESUMO
OBJECTIVE: Understanding residual brain function in disorders of consciousness poses extraordinary challenges, and imaging examinations are needed to complement clinical assessment. The default-mode network (DMN) is known to be dysfunctional, although correlation with level of consciousness remains controversial. We investigated DMN activity with resting-state functional magnetic resonance imaging (rs-fMRI), alongside its structural and metabolic integrity, aiming to elucidate the corresponding associations with clinical assessment. METHODS: We enrolled 119 consecutive patients: 72 in a vegetative state/unresponsive wakefulness state (VS/UWS), 36 in a minimally conscious state (MCS), and 11 with severe disability. All underwent structural MRI and rs-fMRI, and a subset also underwent 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET). Data were analyzed with manual and automatic approaches, in relation to diagnosis and clinical score. RESULTS: Excluding the quartile with largest head movement, DMN activity was decreased in VS/UWS compared to MCS, and correlated with clinical score. Independent-component and seed-based analyses provided similar results, although the latter and their combination were most informative. Structural MRI and FDG-PET were less sensitive to head movement and had better diagnostic accuracy than rs-fMRI only when all cases were included. rs-fMRI indicated relatively preserved DMN activity in a small subset of VS/UWS patients, 2 of whom evolved to MCS. The integrity of the left hemisphere appears to be predictive of a better clinical status. INTERPRETATION: rs-fMRI of the DMN is sensitive to clinical severity. The effect is consistent across data analysis approaches, but heavily dependent on head movement. rs-fMRI could be informative in detecting residual DMN activity for those patients who remain relatively still during scanning and whose diagnosis is uncertain. Ann Neurol 2016;79:841-853.
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Primary malignant tumors of the aorta are extremely rare, and the diagnosis is difficult from the clinical onset. Accordingly to the principles of cancer surgery, "en bloc" resection of the tumor-involved aorta and graft interposition is the gold standard, but it is still technically challenging and comorbidities may rule out some patients from an operative treatment. Thoracic endovascular aortic repair has been reported anecdotally, but it is an ease and rapid alternative in urgent circumstances and proved to be effective to relieve symptoms caused by these lesions. Unfortunately, no matter what is the type of histology or immunohistochemistry, or the type of treatment, the prognosis of aortic malignancies is very poor. Nevertheless, an operative treatment strategy which includes surgical resection and chemotherapy or radiation had long survival than patients treated with a single modality. We report a case of acute mesenteric syndrome caused by an occlusive and embolizing thrombus of the descending thoracic aorta caused by primary aortic sarcoma treated with thoracic endovascular aortic repair.
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Aorta Torácica/cirurgia , Doenças da Aorta/cirurgia , Arteriopatias Oclusivas/cirurgia , Implante de Prótese Vascular , Embolia/cirurgia , Procedimentos Endovasculares , Sarcoma/complicações , Neoplasias Vasculares/complicações , Idoso , Aorta Torácica/patologia , Doenças da Aorta/diagnóstico por imagem , Doenças da Aorta/etiologia , Aortografia/métodos , Arteriopatias Oclusivas/diagnóstico por imagem , Arteriopatias Oclusivas/etiologia , Prótese Vascular , Implante de Prótese Vascular/instrumentação , Angiografia por Tomografia Computadorizada , Embolia/diagnóstico por imagem , Embolia/etiologia , Procedimentos Endovasculares/instrumentação , Humanos , Masculino , Isquemia Mesentérica/etiologia , Isquemia Mesentérica/cirurgia , Oclusão Vascular Mesentérica/etiologia , Oclusão Vascular Mesentérica/cirurgia , Desenho de Prótese , Sarcoma/patologia , Resultado do Tratamento , Neoplasias Vasculares/patologiaRESUMO
BACKGROUND: To analyze the predictors and describe the outcomes of cross-clamp intolerance (CCI) and the results of the use of carotid endarterectomy (CEA) with shunting or a shift strategy to immediate carotid artery stenting (CAS) in this setting. METHODS: Between January 2008 and December 2015, 385 patients were elected for single-sided, isolated CEA under locoregional anesthesia. In case of CCI, CEA with shunt was used selectively, whereas indication to immediate conversion to CAS was the immediate onset and severe persistent deterioration of the neurologic status, and/or local technical difficulties to perform endarterectomy. Primary outcome was prevention of death and all early (<30 days) perioperative cerebrovascular events. RESULTS: We treated 169 (43.9%) symptomatic lesions; urgent (≤48 hours) intervention was performed in 85 (22.1%) cases. Carotid CCI occurred in 45 (11.7%) patients. CEA with shunt was used in 16, whereas CAS in 27 (7.0%, 2 refused further treatment). Multivariable analysis identified hypertension (odds ratio [OR]: 2.93, 95% confidence interval [CI]: 1.01-8.52; P = 0.049) and symptomatic lesions (OR: 2.34, 95% CI: 1.11-4.93; P = 0.025) as significant predictors of CCI. In-hospital mortality rate was 0.5%; none occurred in CCI group. Postoperative cerebrovascular event rate was 2.3% (n = 9). At multivariable analyses, only CCI (OR: 6.60, 95% CI: 1.65-26.36; P = 0.008) was significantly associated with postoperative cerebrovascular events, with no significant different clinical outcomes between CEA and CAS. CONCLUSIONS: Hypertension and symptomatic carotid stenosis were significant predictors of CCI, which was found to be predictive for postoperative cerebrovascular events. In selected patients with CCI, CAS had satisfactory, similar results of CEA.
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Anestesia por Condução , Estenose das Carótidas/cirurgia , Circulação Cerebrovascular , Endarterectomia das Carótidas , Idoso , Idoso de 80 Anos ou mais , Anestesia por Condução/efeitos adversos , Anestesia por Condução/mortalidade , Estenose das Carótidas/complicações , Estenose das Carótidas/mortalidade , Estenose das Carótidas/fisiopatologia , Transtornos Cerebrovasculares/etiologia , Transtornos Cerebrovasculares/fisiopatologia , Distribuição de Qui-Quadrado , Constrição , Endarterectomia das Carótidas/efeitos adversos , Endarterectomia das Carótidas/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Hipertensão/complicações , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: The study compared the metric characteristics (discriminant capacity and factorial structure) of two different methods for scoring the items of the Coma Recovery Scale-Revised and it analysed scale scores collected using the standard assessment procedure and a new proposed method. DESIGN: Cross sectional design/methodological study. SETTING: Inpatient, neurological unit. PARTICIPANTS: A total of 153 patients with disorders of consciousness were consecutively enrolled between 2011 and 2013. INTERVENTION: All patients were assessed with the Coma Recovery Scale-Revised using standard (rater 1) and inverted (rater 2) procedures. MAIN OUTCOME MEASURES: Coma Recovery Scale-Revised score, number of cognitive and reflex behaviours and diagnosis. RESULTS: Regarding patient assessment, rater 1 using standard and rater 2 using inverted procedures obtained the same best scores for each subscale of the Coma Recovery Scale-Revised for all patients, so no clinical (and statistical) difference was found between the two procedures. In 11 patients (7.7%), rater 2 noted that some Coma Recovery Scale-Revised codified behavioural responses were not found during assessment, although higher response categories were present. A total of 51 (36%) patients presented the same Coma Recovery Scale-Revised scores of 7 or 8 using a standard score, whereas no overlap was found using the modified score. Unidimensionality was confirmed for both score systems. CONCLUSION: The Coma Recovery Scale Modified Score showed a higher discriminant capacity than the standard score and a monofactorial structure was also supported. The inverted assessment procedure could be a useful evaluation method for the assessment of patients with disorder of consciousness diagnosis.
Assuntos
Coma/fisiopatologia , Coma/psicologia , Escala de Gravidade do Ferimento , Recuperação de Função Fisiológica , Coma/etiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria , Curva ROCRESUMO
Odor detection sensitivity can be rapidly altered by fear conditioning; whether this effect is augmented over time is not known. The present study aimed to test whether repeated conditioning sessions induce changes in odor detection threshold as well as in conditioned responses and whether olfactory stimuli evoke stronger conditioned responses than visual stimuli. The repeated conditioning group participated in repeated sessions over 2 weeks whereas the single conditioning group participated in 1 conditioning session; both groups were presented with visual and olfactory stimuli, were paired with an electric shock (CS+) and 2 matched control stimuli not paired with shock (CS-) while olfactory detection threshold and skin conductance responses (SCRs) were measured before and after the last session. We found increased sensitivity for the CS+ odor in the repeated but not in the single conditioning group, consistent with changes in olfactory sensitivity following repeated aversive learning and of a similar magnitude to what has previously been demonstrated in the periphery. SCR to the visual and olfactory CS+ were similar between groups, indicating that sensory thresholds can change without corresponding change in conditioned responses. In conclusion, repeated conditioning increases detection sensitivity and reduces conditioned responses, suggesting that segregated processes influence perception and conditioned responses.
Assuntos
Condicionamento Clássico/fisiologia , Medo/fisiologia , Odorantes , Estimulação Luminosa , Adulto , Feminino , Humanos , Masculino , Adulto JovemRESUMO
In the past 2 decades, several attempts have been made to promote a correct diagnosis and possible restorative interventions in patients suffering from disorders of consciousness. Sensory stimulation has been proved to be useful in sustaining the level of arousal/awareness and to improve behavioural responsiveness with a significant effect on oro-motor functions. Recently, action observation has been proposed as a stimulation strategy in patients with disorders of consciousness, based on neurophysiological evidence that the motor cortex can be activated not only during action execution but also when actions are merely observed in the absence of motor output, or during listening to action sounds and speech. This mechanism is provided by the activity of mirror neurons. In the present study, a group of patients with disorders of consciousness (11 males, 4 females; median age: 55 years; age range: 19-74 years) underwent task-based functional MRI in which they had, in one condition, to observe and listen to the sound of mouth actions, and in another condition, to listen to verbs with motor or abstract content. In order to verify the presence of residual activation of the mirror neuron system, the brain activations of patients were compared with that of a group of healthy individuals (seven males, eight females; median age: 33.4 years; age range: 24-65 years) performing the same tasks. The results show that brain activations were lower in patients with disorders of consciousness compared with controls, except for primary auditory areas. During the audiovisual task, 5 out of 15 patients with disorders of consciousness showed only residual activation of low-level visual and auditory areas. Activation of high-level parieto-premotor areas was present in six patients. During the listening task, three patients showed only low-level activations, and six patients activated also high-level areas. Interestingly, in both tasks, one patient with a clinical diagnosis of vegetative state showed activations of high-level areas. Region of interest analysis on blood oxygen level dependent signal change in temporal, parietal and premotor cortex revealed a significant linear relation with the level of clinical functioning, assessed with coma recovery scale-revised. We propose a classification of the patient's response based on the presence of low-level and high-level activations, combined with the patient's functional level. These findings support the use of action observation and listening as possible stimulation strategies in patients with disorders of consciousness and highlight the relevance of combined methods based on functional assessment and brain imaging to provide more detailed neuroanatomical specificity about residual activated areas at both cortical and subcortical levels.