RESUMEN
BACKGROUND: Spinal cord damage is a feature of many spinocerebellar ataxias (SCAs), but well-powered in vivo studies are lacking and links with disease severity and progression remain unclear. Here we characterise cervical spinal cord morphometric abnormalities in SCA1, SCA2, SCA3 and SCA6 using a large multisite MRI dataset. METHODS: Upper spinal cord (vertebrae C1-C4) cross-sectional area (CSA) and eccentricity (flattening) were assessed using MRI data from nine sites within the ENIGMA-Ataxia consortium, including 364 people with ataxic SCA, 56 individuals with preataxic SCA and 394 nonataxic controls. Correlations and subgroup analyses within the SCA cohorts were undertaken based on disease duration and ataxia severity. RESULTS: Individuals in the ataxic stage of SCA1, SCA2 and SCA3, relative to non-ataxic controls, had significantly reduced CSA and increased eccentricity at all examined levels. CSA showed large effect sizes (d>2.0) and correlated with ataxia severity (r<-0.43) and disease duration (r<-0.21). Eccentricity correlated only with ataxia severity in SCA2 (r=0.28). No significant spinal cord differences were evident in SCA6. In preataxic individuals, CSA was significantly reduced in SCA2 (d=1.6) and SCA3 (d=1.7), and the SCA2 group also showed increased eccentricity (d=1.1) relative to nonataxic controls. Subgroup analyses confirmed that CSA and eccentricity are abnormal in early disease stages in SCA1, SCA2 and SCA3. CSA declined with disease progression in all, whereas eccentricity progressed only in SCA2. CONCLUSIONS: Spinal cord abnormalities are an early and progressive feature of SCA1, SCA2 and SCA3, but not SCA6, which can be captured using quantitative MRI.
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Imagen por Resonancia Magnética , Ataxias Espinocerebelosas , Humanos , Ataxias Espinocerebelosas/diagnóstico por imagen , Ataxias Espinocerebelosas/patología , Ataxias Espinocerebelosas/genética , Masculino , Femenino , Persona de Mediana Edad , Adulto , Genotipo , Anciano , Médula Espinal/patología , Médula Espinal/diagnóstico por imagen , Médula Cervical/diagnóstico por imagen , Médula Cervical/patología , Índice de Severidad de la Enfermedad , Estudios de Casos y ControlesRESUMEN
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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Esclerosis Amiotrófica Lateral , Proteína C9orf72 , Imagen por Resonancia Magnética , Mutación , Pulvinar , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Amiotrófica Lateral/genética , Esclerosis Amiotrófica Lateral/diagnóstico por imagen , Esclerosis Amiotrófica Lateral/fisiopatología , Esclerosis Amiotrófica Lateral/patología , Proteína C9orf72/genética , Demencia Frontotemporal/genética , Demencia Frontotemporal/fisiopatología , Demencia Frontotemporal/diagnóstico por imagen , Demencia Frontotemporal/patología , Heterocigoto , Pulvinar/diagnóstico por imagen , Pulvinar/fisiopatología , Pulvinar/patologíaRESUMEN
PURPOSE: Spinocerebellar ataxia SCA1 and SCA2 are adult-onset hereditary disorders, due to triplet CAG expansion in their respective causative genes. The pathophysiology of SCA1 and SCA2 suggests alterations of cerebello-thalamo-cortical pathway and its connections to the basal ganglia. In this framework, thalamic integrity is crucial for shaping efficient whole-brain dynamics and functions. The aims of the study are to identify structural changes in thalamic nuclei in presymptomatic and symptomatic SCA1 and SCA2 patients and to assess disease progression within a 1-year interval. MATERIAL AND METHODS: A prospective 1-year clinical and MRI assessment was conducted in 27 presymptomatic and 23 clinically manifest mutation carriers for SCA1 and SCA2 expansions. Cross-sectional and longitudinal changes of thalamic nuclei volume were investigated in SCA1 and SCA2 individuals and in healthy participants (n = 20). RESULTS: Both SCA1 and SCA2 patients had significant atrophy in the majority of thalamic nuclei, except for the posterior and partly medial nuclei. The 1-year longitudinal evaluation showed a specific pattern of atrophy in ventral and posterior thalamus, detectable even at the presymptomatic stage of the disease. CONCLUSION: For the first time in vivo, our exploratory study has shown that different thalamic nuclei are involved at different stages of the degenerative process in both SCA1 and SCA2. It is therefore possible that thalamic alterations might significantly contribute to the progression of the disease years before overt clinical manifestations occur.
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Progresión de la Enfermedad , Imagen por Resonancia Magnética , Ataxias Espinocerebelosas , Tálamo , Humanos , Masculino , Femenino , Ataxias Espinocerebelosas/diagnóstico por imagen , Ataxias Espinocerebelosas/patología , Ataxias Espinocerebelosas/genética , Adulto , Estudios Prospectivos , Persona de Mediana Edad , Imagen por Resonancia Magnética/métodos , Tálamo/diagnóstico por imagen , Tálamo/patología , Estudios Transversales , Atrofia/diagnóstico por imagen , Ataxina-1/genética , Estudios Longitudinales , Ataxina-2/genética , Tamaño de los ÓrganosRESUMEN
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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Cefaleas Secundarias , Atención Plena , Humanos , Atención Plena/métodos , Cefaleas Secundarias/terapia , Cefaleas Secundarias/psicología , Femenino , Masculino , Adulto , Persona de Mediana Edad , Estudios Longitudinales , Método Simple Ciego , Imagen por Resonancia Magnética , Red en Modo Predeterminado/diagnóstico por imagen , Red en Modo Predeterminado/fisiopatología , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/fisiopatologíaRESUMEN
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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Cefalalgia Histamínica , Humanos , Cefalalgia Histamínica/terapia , Dolor , Cefalea , Hipotálamo/diagnóstico por imagen , Compuestos de LitioRESUMEN
BACKGROUND AND OBJECTIVES: Spinocerebellar ataxias (SCAs) are autosomal dominant disorders with extensive clinical and genetic heterogeneity. We recently identified a form of SCA transmitted with a digenic pattern of inheritance caused by the concomitant presence of an intermediate-length expansion in TATA-box binding protein gene (TBP40-46 ) and a heterozygous pathogenic variant in the Stip1-homologous and U-Box containing protein 1 gene (STUB1). This SCATBP/STUB1 represents the first example of a cerebellar disorder in which digenic inheritance has been identified. OBJECTIVES: We studied a large cohort of patients with SCATBP/STUB1 with the aim of describing specific clinical and neuroimaging features of this distinctive genotype. METHODS: In this observational study, we recruited 65 affected and unaffected family members from 21 SCATBP/STUB1 families and from eight families with monogenic SCA17. Their characteristics and phenotypes were compared with those of 33 age-matched controls. RESULTS: SCATBP/STUB1 patients had multi-domain dementia with a more severe impairment in respect to patient carrying only fully expanded SCA17 alleles. Cerebellar volume and thickness of cerebellar cortex were reduced in SCATBP/STUB1 compared with SCA17 patients (P = 0.03; P = 0.008). Basal ganglia volumes were reduced in both patient groups, as compared with controls, whereas brainstem volumes were significantly reduced in SCATBP/STUB1 , but not in SCA17 patients. CONCLUSIONS: The identification of the complex SCATBP/STUB1 phenotype may impact on diagnosis and genetic counseling in the families with both hereditary and sporadic ataxia. The independent segregation of TBP and STUB1 alleles needs to be considered for recurrence risk and predictive genetic tests. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Ataxia , Demencia , Ataxias Espinocerebelosas , Humanos , Ataxia/genética , Demencia/genética , Genotipo , Fenotipo , Ataxias Espinocerebelosas/diagnóstico por imagen , Ataxias Espinocerebelosas/genética , Ataxias Espinocerebelosas/metabolismo , Proteína de Unión a TATA-Box/genética , Proteína de Unión a TATA-Box/metabolismo , Expansión de Repetición de Trinucleótido , Ubiquitina-Proteína Ligasas/genéticaRESUMEN
BACKGROUND: Mindfulness gained considerable attention for migraine management, but RCTs are lacking. We aimed to assess the efficacy of a six-sessions mindfulness-based treatment added to treatment as usual (TaU) in patients with Chronic Migraine (CM) and Medication Overuse Headache (MOH) on headache frequency, medication intake, quality of life, disability, depression and anxiety, cutaneous allodynia, awareness of inner states, work-related difficulties, and disease cost. METHODS: In this Phase-III single-blind RCT carried out in a specialty Italian headache center, 177 patients with CM and MOH were randomized 1:1 to either TaU (withdrawal from overused drugs, education on proper medication use and lifestyle issues, and tailored prophylaxis) or mindfulness-based intervention added to TaU (TaU + MIND). The mindfulness-based intervention consisted of six group session of mindfulness practice and 7-10 min daily self-practice. The primary endpoint was the achievement of ≥ 50% headache frequency reduction at 12 months compared to baseline, and was analyzed on an intention-to-treat principle using Pearson's Chi-Squared test. Secondary endpoints included medication intake, quality of life (QoL), disability, depression and anxiety, cutaneous allodynia, awareness of inner states, work-related difficulties, and disease cost. The secondary endpoints were analyzed using per-protocol linear mixed models. RESULTS: Out of the 177 participants 89 were randomized to TaU and 88 to TaU + MIND. Patients in the TaU + MIND group outperformed those in TaU for the primary endpoint (78.4% vs. 48.3%; p < 0.0001), and showed superior improvement in headache frequency, QoL and disability, headache impact, loss of productive time, medication intake, and in total, indirect and direct healthcare costs. CONCLUSIONS: A mindfulness-based treatment composed of six-week session and 7-10 min daily self-practice added on to TaU is superior to TaU alone for the treatment of patients with CM and MOH. TRIAL REGISTRATION: MIND-CM was registered on clinicaltrials.gov (NCT03671681) on14/09/2018.
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Cefaleas Secundarias , Trastornos Migrañosos , Atención Plena , Humanos , Atención Plena/métodos , Calidad de Vida , Resultado del Tratamiento , Método Simple Ciego , Hiperalgesia , Trastornos Migrañosos/tratamiento farmacológico , Cefalea , Cefaleas Secundarias/tratamiento farmacológicoRESUMEN
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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Dolor Crónico/diagnóstico por imagen , Dolor Crónico/fisiopatología , Neuroimagen Funcional , Corteza Insular/diagnóstico por imagen , Corteza Insular/fisiopatología , HumanosRESUMEN
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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Lesiones Encefálicas , Estado de Conciencia , Atrofia , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Lesiones Encefálicas/patología , Estudios Transversales , Electroencefalografía , Humanos , Imagen por Resonancia Magnética/métodosRESUMEN
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 Espinocerebelosas , Adulto , Progresión de la Enfermedad , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , Estudios Prospectivos , Ataxias Espinocerebelosas/complicaciones , Ataxias Espinocerebelosas/diagnóstico por imagen , Ataxias Espinocerebelosas/genéticaRESUMEN
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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Cefalalgia Histamínica , Corteza Cerebelosa , Adelgazamiento de la Corteza Cerebral , Cefalalgia Histamínica/diagnóstico por imagen , Estudios Transversales , Humanos , Imagen por Resonancia Magnética/métodosRESUMEN
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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Cefalalgia Histamínica , Trastornos de Cefalalgia , Amígdala del Cerebelo/diagnóstico por imagen , Encéfalo , Cefalalgia Histamínica/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética/métodos , Vías Nerviosas/diagnóstico por imagen , DolorRESUMEN
This article describes a case of Foreign accent syndrome (FAS) in an Italian woman who developed a Canadian-like foreign accent without brain damage (functional FAS). The patient underwent an in-depth neuroimaging and (neuro)psychological evaluation. Language networks in the frontotemporal-parietal areas were typically activated bilaterally through fMRI and MEG assessments based on task-based data. Resting-state fMRI showed preserved connectivity between language areas. An obsessive-compulsive personality profile and mild anxiety were found, suggesting psychological and psychiatric factors may be relevant. Accordingly with our findings, multimodal imaging is beneficial to understand FAS neurological and functional etiologies.
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Lenguaje , Imagen por Resonancia Magnética , Femenino , Humanos , Canadá , Imagen por Resonancia Magnética/métodos , Imagen MultimodalRESUMEN
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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Adaptación Fisiológica/fisiología , Ceguera/fisiopatología , Mapeo Encefálico , Color , Formación de Concepto/fisiología , Recuerdo Mental/fisiología , Lóbulo Occipital/fisiología , Percepción del Habla/fisiología , Lóbulo Temporal/fisiología , Adulto , Ceguera/congénito , Percepción de Color/fisiología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana EdadRESUMEN
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 Conciencia , Estado Vegetativo Persistente , Humanos , Imagen por Resonancia Magnética , Neuroimagen , Tomografía de Emisión de Positrones , Percepción VisualRESUMEN
Isocitrate dehydrogenase 1/2 (IDH1/2) mutations are often detected in lower-grade gliomas (LGG) and result into 2-hydroxyglutarate (2HG) synthesis. Prior studies showed that 2HG can be detected in vivo using magnetic resonance spectroscopy (MRS), but its accuracy and translational impact are still under investigation. PURPOSE: To investigate the clinical feasibility of MRS for in vivo detection and quantification of 2HG on consecutive treatment-naïve suspect LGG patients and to compare MRS accuracy with tissue IDH1/2 analysis. METHODS: MRS spectra at 3 T were acquired with 1H-MRS single-voxel PRESS 2HG-tailored sequences with TE 30 (group 1) or TE 97 (groups 2A and B). Voxel sizes were 1.5 × 1.5 × 1.5 cm3 for group 1 (n = 13) and group 2A (n = 14) and 2 × 2 × 2 cm3 for group 2B (n = 32). Multiple metabolites' concentrations were analyzed with LCModel. Tumors were assessed for IDH status and main molecular markers. 2HG levels in urine/blood were measured by liquid chromatography-mass spectrometry. RESULTS: The larger voxel TE 97 sequence resulted in highest specificity (100%), sensitivity (79%), and accuracy (87%). Urine and blood 2HG did not result predictive. CONCLUSION: Our data confirm that 2 × 2 × 2-cm3 voxel TE 97 MRS shows high accuracy for 2HG detection, with good sensitivity and 100% specificity in distinguishing IDH mutant gliomas. Main limits of the technique are small tumor volume and low cellularity. Integrating 2HG-MRS with other metabolites may help non-invasive diagnosis of glioma, prognostic assessment, and treatment planning in clinical setting.
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Glioma/tratamiento farmacológico , Glioma/patología , Glutaratos/farmacología , Espectroscopía de Protones por Resonancia Magnética , Biomarcadores/análisis , Estudios de Factibilidad , Femenino , Humanos , Isocitrato Deshidrogenasa/genética , Espectroscopía de Resonancia Magnética/métodos , Masculino , Pronóstico , Espectroscopía de Protones por Resonancia Magnética/métodosRESUMEN
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 imagen , Cefalalgia Histamínica/fisiopatología , Vías Nerviosas/fisiopatología , Neuroimagen , Cefalalgia Histamínica/diagnóstico por imagen , Estimulación Encefálica Profunda/métodos , Humanos , Imagen por Resonancia Magnética/métodos , Neuroimagen/métodosRESUMEN
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/fisiopatología , Cefalalgia Histamínica/fisiopatología , Vías Nerviosas/fisiopatología , Adulto , Encéfalo/diagnóstico por imagen , Cefalalgia Histamínica/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Vías Nerviosas/diagnóstico por imagenRESUMEN
Pain assessment in patients with disorders of consciousness (DoC) is a controversial issue for clinicians, who require tools and standardised procedures for testing nociception in non-communicative patients. The aims of the present study were, first, to analyse the psychometric properties of the Italian version of the Nociception Coma Scale and, second, to evaluate pressure pain thresholds in a group of patients with DoC. The authors conducted a multi-centre study on 40 healthy participants and 60 DoC patients enrolled from six hospitals in Italy. For each group an electronic algometer was used to apply all nociceptive pressure stimuli. Our results show that the Italian version of the NCS retains the good psychometric properties of the original version and is therefore suitable for standardised pain assessment in clinical practice. In our study, pressure pain thresholds measured in a group of patients in vegetative and minimally conscious state were relatively lower than pain threshold values found in a group of healthy participants. Such findings motivate additional investigation on possible pain sensitisation in patients with severe brain injury and multiple co-morbidities, and on application of tailored therapeutic approaches useful for pain management in patients unable verbally to communicate their feelings.
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Trastornos de la Conciencia/diagnóstico , Trastornos de la Conciencia/fisiopatología , Dimensión del Dolor , Umbral del Dolor , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dolor Nociceptivo/diagnóstico , Dolor Nociceptivo/fisiopatología , Variaciones Dependientes del Observador , Presión , Psicometría , Sensibilidad y EspecificidadRESUMEN
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.