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Visual hallucinations in Lewy body disease (LBD) can be differentiated based on phenomenology into minor phenomena (MVH) and complex hallucinations (CVH). MVH include a variety of phenomena, such as illusions, presence and passage hallucinations occurring at early stages of LBD. The neural mechanisms of visual hallucinations are largely unknown. The hodotopic model posits that the hallucination state is due to abnormal activity in specialized visual areas, that occurs in the context of wider network connectivity alterations and that phenomenology of VH, including content and temporal characteristics, may help identify brain regions underpinning these phenomena. Here we investigated both the topological and hodological neural basis of visual hallucinations integrating grey and white matter imaging analyses. We studied LBD patients with VH and age matched healthy controls (HC). VH were assessed using a North-East-Visual-Hallucinations-Interview that captures phenomenological detail. Then we applied voxel-based morphometry and tract based spatial statistics approaches to identify grey and white matter changes. First, we compared LBD patients and HC. We found a reduced grey matter volume and a widespread damage of white tracts in LBD compared to HC. Then we tested the association between CVH and MVH and grey and white matter indices. We found that CVH duration was associated with decreased grey matter volume in the fusiform gyrus suggesting that LBD neurodegeneration-related abnormal activity in this area is responsible for CVH. An unexpected finding was that MVH severity was associated with a greater integrity of white matter tracts, specifically those connecting dorsal, ventral attention networks and visual areas. Our results suggest that networks underlying MVH need to be partly intact and functional for MVH experiences to occur, while CVH occur when cortical areas are damaged. The findings support the hodotopic view and the hypothesis that MVH and CVH relate to different neural mechanisms, with wider implications for the treatment of these symptoms in a clinical context.
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Sustancia Gris , Alucinaciones , Enfermedad por Cuerpos de Lewy , Sustancia Blanca , Humanos , Alucinaciones/fisiopatología , Alucinaciones/etiología , Alucinaciones/diagnóstico por imagen , Enfermedad por Cuerpos de Lewy/fisiopatología , Enfermedad por Cuerpos de Lewy/patología , Enfermedad por Cuerpos de Lewy/diagnóstico por imagen , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Sustancia Gris/fisiopatología , Femenino , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Sustancia Blanca/fisiopatología , Masculino , Anciano , Imagen por Resonancia Magnética , Anciano de 80 o más Años , Estudios de Casos y Controles , Persona de Mediana EdadRESUMEN
Objectives: Recent studies supported coagulation involvement in multiple sclerosis, an inflammatory-demyelinating and degenerative disease of the central nervous system. The main objectives of this observational study were to identify the most specific pro-coagulative/vascular factors for multiple sclerosis pathogenesis and to correlate them with brain hemodynamic abnormalities. Methods: We compared i) serum/plasma levels of complement(C)/coagulation/vascular factors, viral/microbiological assays, fat-soluble vitamins and lymphocyte count among people with multiple sclerosis sampled in a clinical remission (n=30; 23F/7M, 40 ± 8.14 years) or a relapse (n=30; 24F/6M, age 41 ± 10.74 years) and age/sex-matched controls (n=30; 23F/7M, 40 ± 8.38 years); ii) brain hemodynamic metrics at dynamic susceptibility contrast-enhanced 3T-MRI during relapse and remission, and iii) laboratory data with MRI perfusion metrics and clinical features of people with multiple sclerosis. Two models by Partial Least Squares Discriminant Analysis were performed using two groups as input: (1) multiple sclerosis vs. controls, and (2) relapsing vs. remitting multiple sclerosis. Results: Compared to controls, multiple sclerosis patients had a higher Body-Mass-Index, Protein-C and activated-C9; and a lower activated-C4. Levels of Tissue-Factor, Tie-2 and P-Selectin/CD62P were lower in relapse compared to remission and HC, whereas Angiopoietin-I was higher in relapsing vs. remitting multiple sclerosis. A lower number of total lymphocytes was found in relapsing multiple sclerosis vs. remitting multiple sclerosis and controls. Cerebral-Blood-Volume was lower in normal-appearing white matter and left caudatum while Cerebral-Blood-Flow was inferior in bilateral putamen in relapsing versus remitting multiple sclerosis. The mean-transit-time of gadolinium-enhancing lesions negatively correlated with Tissue-Factor. The top-5 discriminating variables for model (1) were: EBV-EBNA-1 IgG, Body-Mass-Index, Protein-C, activated-C4 and Tissue-Factor whereas for model (2) were: Tissue-Factor, Angiopoietin-I, MCHC, Vitamin A and T-CD3. Conclusion: Tissue-factor was one of the top-5 variables in the models discriminating either multiple sclerosis from controls or multiple sclerosis relapse from remission and correlated with mean-transit-time of gadolinium-enhancing lesions. Tissue-factor appears a promising pro-coagulative/vascular biomarker and a possible therapeutic target in relapsing-remitting multiple sclerosis. Clinical trial registration: ClinicalTrials.gov, identifier NCT04380220.
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Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Adulto , Humanos , Persona de Mediana Edad , Gadolinio/uso terapéutico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Recurrencia , TromboplastinaRESUMEN
BACKGROUND: Despite obesity being well known to be associated with several pituitary hormone imbalances, pituitary appearance in magnetic resonance imaging (MRI) in patients with obesity is understudied. OBJECTIVE: To evaluate the pituitary volume and signal intensity at MRI in patients with obesity. METHODS: This is a prospective study performed in an endocrine Italian referral center (ClinicalTrial.gov Identifier: NCT03458533). Sixty-nine patients with obesity (BMI > 30 kg/m2) and twenty-five subjects without obesity were enrolled. Thirty-three patients with obesity were re-evaluated after 3 years of diet and lifestyle changes, of whom 17 (51.5%) achieved a > 5% loss of their initial body weight, whereas the remaining 16 (48.5%) had maintained or gained weight. Evaluations included metabolic and hormone assessments, DEXA scan, and pituitary MRI. Pituitary signal intensity was quantified by measuring the pixel density using ImageJ software. RESULTS: At baseline, no difference in pituitary volume was observed between the obese and non-obese cohorts. At the 3-year follow-up, pituitary volume was significantly reduced (p = 0.011) only in participants with stable-increased body weight. Furthermore, a significant difference was noted in the mean pituitary intensity of T1-weighted plain and contrast-enhanced sequences between the obese and non-obese cohorts at baseline (p = 0.006; p = 0.002), and a significant decrease in signal intensity was observed in the subgroup of participants who had not lost weight (p = 0.012; p = 0.017). Insulin-like growth factor-1 levels, following correction for BMI, were correlated with pituitary volume (p = 0.001) and intensity (p = 0.049), whereas morning cortisol levels were correlated with pituitary intensity (p = 0.007). The T1-weighted pituitary intensity was negatively correlated with truncal fat (p = 0.006) and fibrinogen (p = 0.018). CONCLUSIONS: The CHIASM study describes a quantitative reduction in pituitary intensity in T1-weighted sequences in patients with obesity. These alterations could be explained by changes in the pituitary stromal tissue, correlated with low-grade inflammation.
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Obesidad , Aumento de Peso , Humanos , Estudios Prospectivos , Obesidad/diagnóstico por imagen , Fibrinógeno , InflamaciónRESUMEN
Background: The migrainous aura has different clinical phenotypes. While the various clinical differences are well-described, little is known about their neurophysiological underpinnings. To elucidate the latter, we compared white matter fiber bundles and gray matter cortical thickness between healthy controls (HC), patients with pure visual auras (MA) and patients with complex neurological auras (MA+). Methods: 3T MRI data were collected between attacks from 20 patients with MA and 15 with MA+, and compared with those from 19 HCs. We analyzed white matter fiber bundles using tract-based spatial statistics (TBSS) of diffusion tensor imaging (DTI) and cortical thickness with surface-based morphometry of structural MRI data. Results: Tract-based spatial statistics showed no significant difference in diffusivity maps between the three subject groups. As compared to HCs, both MA and MA+ patients had significant cortical thinning in temporal, frontal, insular, postcentral, primary and associative visual areas. In the MA group, the right high-level visual-information-processing areas, including lingual gyrus, and the Rolandic operculum were thicker than in HCs, while in the MA+ group they were thinner. Discussion: These findings show that migraine with aura is associated with cortical thinning in multiple cortical areas and that the clinical heterogeneity of the aura is reflected by opposite thickness changes in high-level visual-information-processing, sensorimotor and language areas.
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The role of the hypothalamus and the limbic system at the onset of a migraine attack has recently received significant interest. We analyzed diffusion tensor imaging (DTI) parameters of the entire hypothalamus and its subregions in 15 patients during a spontaneous migraine attack and in 20 control subjects. We also estimated the non-linear measure resting-state functional MRI BOLD signal's complexity using Higuchi fractal dimension (FD) and correlated DTI/fMRI findings with patients' clinical characteristics. In comparison with healthy controls, patients had significantly altered diffusivity metrics within the hypothalamus, mainly in posterior ROIs, and higher FD values in the salience network (SN). We observed a positive correlation of the hypothalamic axial diffusivity with migraine severity and FD of SN. DTI metrics of bilateral anterior hypothalamus positively correlated with the mean attack duration. Our results show plastic structural changes in the hypothalamus related to the attacks severity and the functional connectivity of the SN involved in the multidimensional neurocognitive processing of pain. Plastic changes to the hypothalamus may play a role in modulating the duration of the attack.
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Imagen de Difusión Tensora , Trastornos Migrañosos , Humanos , Imagen de Difusión Tensora/métodos , Trastornos Migrañosos/diagnóstico por imagen , Imagen por Resonancia Magnética , Hipotálamo/diagnóstico por imagen , Plásticos , EncéfaloRESUMEN
Background Subarachnoid hemorrhage (SAH) grading scales typically evaluate a limited number of cisterns on the axial plane. The goal of our study is to apply a simple quantitative yet comprehensive SAH grading scale to all major intracranial cisterns, including the infratentorial cisterns, with multiplanar computed tomography (CT) reformations. Methodology We performed a retrospective review of 94 consecutive cases of spontaneous SAH presenting within 72 hours of onset. SAH was categorized into five grades based on the short-axis thickness of SAH in 20 intracranial cisterns measured on the axial, coronal, and sagittal planes. Statistical analysis was performed for inter-rater agreement with kappa statistics, for inter-plane agreement by Spearman correlation statistics, and for inter-rater and inter-plane agreement by Pearson correlation statistics. Results The extended kappa coefficient for the three reviewers across all 20 cisterns varied from 0.38 (0.27, 0.50) to 0.59 (0.52, 0.65) on the axial plane. The kappa coefficient for two reviewers varied from 0.46 (0.33, 0.59) to 0.70 (0.60, 0.80) on the coronal plane and from 0.35 (0.20, 0.49) to 0.87 (0.77, 0.96) on the sagittal plane. The average grade of cisterns per case demonstrated mostly excellent correlation between the imaging planes with Spearman correlation statistics (≥0.70). Pairwise concordance correlation coefficient of the total SAH score revealed agreement ranging from 0.81 to 0.90 in all three planes. Pearson correlation statistics of the average total SAH scores revealed excellent correlation among the three planes (≥0.91). Conclusion A simple quantitative SAH grading scale can be successfully applied to the supratentorial and infratentorial cisterns in three standard CT imaging planes.
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BACKGROUND: Few studies have evaluated flow diversion with magnetic resonance angiography (MRA). Studies have shown better success of MRA in assessing the aneurysm response, but limited success in assessing stent patency. The patency of arterial branches on MRA remains to be explored. METHODS: Retrospective evaluation of 31 consecutive cases of carotid aneurysms treated with flow diversion was performed with noncontrast time-of-flight (TOF), contrast-enhanced TOF, and cine MRA (time-resolved angiography with interleaved stochastic trajectories) independently by 2 investigators for aneurysm occlusion, stent patency, and arterial branch patency. Digital subtraction angiography served as the gold standard technique. RESULTS: Patients were 6 men and 25 women with a mean ± SD age of 57.8 ± 12.27 years (range, 32-79 years). Stent patency, aneurysm occlusion, and branch patency mostly revealed substantial to perfect interobserver agreement (κ >0.60). Sensitivity, specificity, positive predictive value, and negative predictive value for stent patency on raw data images of TOF were 0.50, 0.86, 0.20, and 0.96 and on contrast-enhanced TOF were 1.0, 0.93, 0.50, and 1.0. Ranges for aneurysm response on the 3 MRA scans were 0.78-0.89 for sensitivity, 0.54-0.92 for specificity, 0.73-0.93 for positive predictive value, and 0.78-0.86 for negative predictive value. Ranges for arterial branch patency among the 3 MRA scans were 0.87-0.96 for sensitivity, 0.50-1.0 for specificity, 0.90-1.0 for positive predictive value, and 0.33-0.80 for negative predictive value. CONCLUSIONS: Aneurysm occlusion, stent patency, and arterial branch patency in flow diversion can be successfully evaluated with the combination of 3 MRA techniques.
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Embolización Terapéutica , Aneurisma Intracraneal , Adulto , Anciano , Angiografía de Substracción Digital/métodos , Embolización Terapéutica/métodos , Femenino , Estudios de Seguimiento , Humanos , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/cirugía , Angiografía por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Visual hallucinations (VH) in Lewy body disease (LBD) have a heterogenous phenomenology classified into minor phenomena (MVH) and complex hallucinations (CVH). Mechanisms underpinning VH and their temporal aspects are largely unknown. According to the hodotopic model, we investigated whether changes in distinct cognitive domains and neural networks in the hallucination trait underpin temporal aspects of MVH and CVH in the hallucination state. 35 LBD patients with VH underwent a complete neuropsychological evaluation and resting-state fMRI. North-East-Visual-Hallucinations-Interview was used to assess their typical VH content, duration, and frequency. We found that MVH was not associated with cognitive impairment, while CVH was associated with impairments in visuoperceptual processes, attention and visual abstract reasoning. In seed-to-seed functional connectivity (FC) analysis we identified functional couplings associated with MVH and CVH temporal severity (duration x frequency), duration and frequency. MVH severity was negatively associated with FC between early visual areas (EVA) and ventral-visual-stream regions, and negatively associated with FC between brainstem and EVA, which may be linked to LBD brainstem neuropathology. CVH duration was positively associated with FC between ventral-visual stream and salience network (SN). CVH frequency was negatively associated with FC between DMN and SN. Functional alterations in distinct visual and attentional networks and their dynamic interaction in trait LBD hallucinators are linked to both the phenomenology of state content and its temporal characteristics. Within a network, VH frequency and duration may be linked to different types of functional alterations: increased connectivity leading to sustained activity prolonging VH (duration) and decreased connectivity increasing dysregulated, spontaneous activity (frequency). These findings support the hodotopic hypothesis of VH and may reflect a link between VH phenomenology, LBD neuropathological progression and the involvement of specific neurotransmitter systems.
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Enfermedad por Cuerpos de Lewy , Atención/fisiología , Alucinaciones/diagnóstico por imagen , Alucinaciones/etiología , Humanos , Enfermedad por Cuerpos de Lewy/complicaciones , Enfermedad por Cuerpos de Lewy/diagnóstico por imagen , Enfermedad por Cuerpos de Lewy/patología , Imagen por Resonancia Magnética , Pruebas NeuropsicológicasRESUMEN
PURPOSE: In subarachnoid hemorrhage, noncontrast CT features are used to guide the localization of ruptured aneurysms on CT angiography and DSA. Multiplanar CT may improve the localization of aneurysm rupture sites over axial plane CT alone. METHODS: Multiplanar CT in three orthogonal planes was used to evaluate 94 cases of SAH. Two investigators independently evaluated each imaging plane for focal thick SAH with mass effect, intracerebral hemorrhage, focal edema, filling defect, subdural hemorrhage, and dominant intraventricular hemorrhage. Also, rupture site was qualitatively identified by combining these variables in each plane and combination of three planes. DSA served as the gold standard to locate the rupture sites. RESULTS: Interobserver agreement was k 0.60 to 0.79 for axial, k 0.43 to 0.86 for coronal and k 0.43 to 0.74 for sagittal planes. Good to substantial agreement was observed for the localization of rupture site in three planes (focal SAH with mass effect - k 0.78 to 0.85; filling defect - k 0.95 to 1.0; intracerebral hemorrhage - k 1.0; focal edema k 1.0; subdural hemorrhage - k 0.61 to 0.83). Dominant intraventricular hemorrhage revealed significant association with DSA to locate ruptured aneurysms (Fisher's exact test - Pr < = P (< 0.001)). With non-missing data, frequency of correct ratings to locate rupture site was 66/67 (99%) in axial plane, 59/66 (89%) in coronal plane, 64/67 (96%) in sagittal plane and 77/77 (100%) in combined 3 planes. CONCLUSIONS: Multiplanar CT head is more successful than axial plane CT alone for the localization of aneurysm rupture sites in SAH.
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Aneurisma Roto , Aneurisma Intracraneal , Hemorragia Subaracnoidea , Aneurisma Roto/complicaciones , Aneurisma Roto/diagnóstico por imagen , Angiografía Cerebral/métodos , Hemorragia Cerebral/complicaciones , Hematoma Subdural , Humanos , Aneurisma Intracraneal/complicaciones , Aneurisma Intracraneal/diagnóstico por imagen , Hemorragia Subaracnoidea/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodosRESUMEN
The hypothalamus has been attributed an important role during the premonitory phase of a migraine attack. Less is known about the role played by the hypothalamus in the interictal period and its relationship with the putative neurocognitive networks previously identified in the pathophysiology of migraine. Our aim was to test whether the hypothalamic microstructure would be altered during the interictal period and whether this co-existed with aberrant connectivity at cortical level. We collected multimodal MRI data from 20 untreated patients with migraine without aura between attacks (MO) and 20 healthy controls (HC) and studied fractional anisotropy, mean (MD), radial (RD), and axial diffusivity of the hypothalamus ROI as a whole from diffusion tensor imaging (DTI). Moreover, we performed an exploratory analysis of the same DTI metrics separately for the anterior and posterior hypothalamic ROIs bilaterally. From resting-state functional MRI, we estimated the Higuchi's fractal dimension (FD), an index of temporal complexity sensible to describe non-periodic patterns characterizing BOLD signature. Finally, we correlated neuroimaging findings with migraine clinical features. In comparison to HC, MO had significantly higher MD, AD, and RD values within the hypothalamus. These findings were confirmed also in the exploratory analysis on the sub-regions of the hypothalamus bilaterally, with the addition of lower FA values on the posterior ROIs. Patients showed higher FD values within the salience network (SN) and the cerebellum, and lower FD values within the primary visual (PV) network compared to HC. We found a positive correlation between cerebellar and SN FD values and severity of migraine. Our findings of hypothalamic abnormalities between migraine attacks may form part of the neuroanatomical substrate that predisposes the onset of the prodromal phase and, therefore, the initiation of an attack. The peculiar fractal dimensionality we found in PV, SN, and cerebellum may be interpreted as an expression of abnormal efficiency demand of brain networks devoted to the integration of sensory, emotional, and cognitive information related to the severity of migraine.
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Hipotálamo/patología , Migraña sin Aura/fisiopatología , Humanos , Hipotálamo/diagnóstico por imagen , Hipotálamo/fisiopatología , Imagen por Resonancia Magnética , Migraña sin Aura/diagnóstico por imagenRESUMEN
BACKGROUND: We searched for differences in resting-state functional connectivity (FC) between brain networks and its relationship with the microstructure of the thalamus between migraine with pure visual auras (MA), and migraine with complex neurological auras (MA+), i.e. with the addition of at least one of sensory or language symptom. METHODS: 3T MRI data were obtained from 20 patients with MA and 15 with MA + and compared with those from 19 healthy controls (HCs). We collected resting state data among independent component networks. Diffusivity metrics of bilateral thalami were calculated and correlated with resting state ICs-Z-scores. RESULTS: As compared to HCs, both patients with MA and MA + disclosed disrupted FC between the default mode network (DMN) and the right dorsal attention system (DAS). The MA + subgroup had lower microstructural metrics than both HCs and the MA subgroup, which correlated negatively with the strength of DMN connectivity. Although the microstructural metrics of MA patients did not differ from those of HCs, these patients lacked the correlation with the strength of DAS connectivity found in HCs. CONCLUSIONS: The present findings suggest that, as far as MRI profiles are concerned, the two clinical phenotypes of migraine with aura have both common and distinct morpho-functional features of nodes in the thalamo-cortical network.
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Epilepsia , Trastornos Migrañosos , Migraña con Aura , Encéfalo , Mapeo Encefálico , Humanos , Imagen por Resonancia Magnética , Migraña con Aura/diagnóstico por imagenRESUMEN
BACKGROUND AND PURPOSE: Using functional magnetic resonance imaging (fMRI), we explored cortical activation in patients with acute Bell's palsy (BP) and analyzed its correlates with clinical status in the acute phase, and with 6-month outcome. METHODS: Twenty-four right-handed patients with acute BP within 15 days of onset and 24 healthy controls underwent fMRI during performance of unilateral active (hemi-smiling) and passive lip movement tasks with both the paretic and the normal lip. The degree of paresis was evaluated during the acute stage and at the 6-month follow up using the House-Brackmann (HB) grading scale. Complete recovery was defined as HB grade II or less at the end of the 6-month period. The difference in the HB grade (ΔHB) between the acute stage and the 6-month follow up was used to evaluate clinical improvement. RESULTS: There were 24 patients with unilateral acute BP. HB grades ranged from III to VI. At 6 months, 11 patients (46%) had completely recovered and 12 (50%) were partially improved. Compared with healthy subjects, BP patients had a significantly greater activation of the frontal areas and the insula ipsilateral to the paretic side. In BP patients, there was an inverse correlation between the activation of the ipsilateral hemisphere when moving the paretic side and the degree of paresis at baseline. An association was also observed between activation and clinical outcome (both complete recovery and ΔHB). CONCLUSIONS: In patients with BP, fMRI may represent a useful tool to predict long-term outcome, guide therapeutic approach, and monitor treatment response.
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Parálisis de Bell/diagnóstico por imagen , Imagen por Resonancia Magnética , Enfermedad Aguda , Adulto , Parálisis de Bell/complicaciones , Parálisis de Bell/fisiopatología , Estudios de Casos y Controles , Humanos , Masculino , Persona de Mediana Edad , Movimiento , Paresia/complicaciones , Adulto JovenRESUMEN
Introduction: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system with an underlying immune-mediated and inflammatory pathogenesis. Innate immunity, in addition to the adaptive immune system, plays a relevant role in MS pathogenesis. It represents the immediate non-specific defense against infections through the intrinsic effector mechanism "immunothrombosis" linking inflammation and coagulation. Moreover, decreased cerebral blood volume (CBV), cerebral blood flow (CBF), and prolonged mean transit time (MTT) have been widely demonstrated by MRI in MS patients. We hypothesized that coagulation/complement and platelet activation during MS relapse, likely during viral infections, could be related to CBF decrease. Our specific aims are to evaluate whether there are differences in serum/plasma levels of coagulation/complement factors between relapsing-remitting (RR) MS patients (RRMS) in relapse and those in remission and healthy controls as well as to assess whether brain hemodynamic changes detected by MRI occur in relapse compared with remission. This will allow us to correlate coagulation status with perfusion and demographic/clinical features in MS patients. Materials and Methods: This is a multi-center, prospective, controlled study. RRMS patients (1° group: 30 patients in relapse; 2° group: 30 patients in remission) and age/sex-matched controls (3° group: 30 subjects) will be enrolled in the study. Patients and controls will be tested for either coagulation/complement (C3, C4, C4a, C9, PT, aPTT, fibrinogen, factor II, VIII, and X, D-dimer, antithrombin, protein C, protein S, von-Willebrand factor), soluble markers of endothelial damage (thrombomodulin, Endothelial Protein C Receptor), antiphospholipid antibodies, lupus anticoagulant, complete blood count, viral serological assays, or microRNA microarray. Patients will undergo dynamic susceptibility contrast-enhanced MRI using a 3.0-T scanner to evaluate CBF, CBV, MTT, lesion number, and volume. Statistical Analysis: ANOVA and unpaired t-tests will be used. The level of significance was set at p ≤ 0.05. Discussion: Identifying a link between activation of coagulation/complement system and cerebral hypoperfusion could improve the identification of novel molecular and/or imaging biomarkers and targets, leading to the development of new effective therapeutic strategies in MS. Clinical Trial Registration: Clinicaltrials.gov, identifier NCT04380220.
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Coagulación Sanguínea/inmunología , Circulación Cerebrovascular , Protocolos Clínicos , Activación de Complemento/inmunología , Esclerosis Múltiple Recurrente-Remitente/sangre , Esclerosis Múltiple Recurrente-Remitente/diagnóstico , Biomarcadores , Factores de Coagulación Sanguínea/metabolismo , Proteínas del Sistema Complemento/inmunología , Proteínas del Sistema Complemento/metabolismo , Susceptibilidad a Enfermedades , Perfilación de la Expresión Génica , Humanos , Imagen por Resonancia Magnética/métodos , Esclerosis Múltiple Recurrente-Remitente/etiologíaRESUMEN
BACKGROUND: Chronic migraine (CM) can be associated with aberrant long-range connectivity of MRI-derived resting-state networks (RSNs). Here, we investigated how the fractal dimension (FD) of blood oxygenation level dependent (BOLD) activity may be used to estimate the complexity of RSNs, reflecting flexibility and/or efficiency in information processing in CM patients respect to healthy controls (HC). METHODS: Resting-state MRI data were collected from 20 untreated CM without history of medication overuse and 20 HC. On both groups, we estimated the Higuchi's FD. On the same subjects, fractional anisotropy (FA) and mean diffusivity (MD) values of bilateral thalami were retrieved from diffusion tensor imaging and correlated with the FD values. RESULTS: CM showed higher FD values within dorsal attention system (DAS) and the anterior part of default-mode network (DMN), and lower FD values within the posterior DMN compared to HC. Although FA and MD were within the range of normality, both correlated with the FD values of DAS. CONCLUSIONS: FD of DAS and DMN may reflect disruption of cognitive control of pain in CM. Since the normal microstructure of the thalamus and its positive connectivity with the cortical networking found in our CM patients reminds similar results obtained assessing the same structures but with the methods of neurophysiology, in episodic migraine during an attack, this may be yet another evidence in supporting CM as a never-ending migraine attack.
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Imagen de Difusión Tensora , Trastornos Migrañosos , Encéfalo , Mapeo Encefálico , Fractales , Hemodinámica , Humanos , Imagen por Resonancia Magnética , Trastornos Migrañosos/diagnóstico por imagenRESUMEN
INTRODUCTION: Trigeminal neuralgia is an exemplary neuropathic pain condition characterized by paroxysmal electric-shock-like pain. However, up to 50% of patients also experiences concomitant continuous pain. In this neuroimaging study, we aimed to identify the specific anatomical features of trigeminal nerve root in patients with concomitant continuous pain. METHODS: We enrolled 73 patients with a definitive diagnosis of classical and idiopathic trigeminal neuralgia and 40 healthy participants. The diagnosis of trigeminal neuralgia was independently confirmed by two clinicians. Patients were grouped as patients with purely paroxysmal pain (45 patients) and patients also with concomitant continuous pain (28 patients). All participants underwent a structured clinical examination and a 3T MRI with sequences dedicated to the anatomical study of the trigeminal nerve root, including volumetric study. Images analysis was independently performed by two investigators, blinded to any clinical data. RESULTS: In most patients with concomitant continuous pain, this type of pain, described as burning, throbbing or aching, manifested at the disease onset. Demographic and clinical variables did not differ between the two groups of patients; the frequency of neurovascular compression and nerve dislocation were similar. Conversely, trigeminal nerve root atrophy was more severe in patients with concomitant continuous pain than in those with purely paroxysmal pain (p = 0.006). CONCLUSIONS: Our clinical and neuroimaging study found that in patients with trigeminal neuralgia, concomitant continuous pain was associated with trigeminal nerve root atrophy, therefore suggesting that this type of pain is likely related to axonal loss and abnormal activity in denervated trigeminal second-order neurons.
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Dolor Facial/patología , Imagen por Resonancia Magnética/métodos , Nervio Trigémino/patología , Neuralgia del Trigémino/patología , Anciano , Atrofia/patología , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuralgia/patología , Estudios Prospectivos , Neuralgia del Trigémino/diagnóstico por imagenRESUMEN
Vitamin K is a fat-soluble nutrient discovered in 1935 and its role in blood coagulation has been thoroughly explored. In recent years, studies conducted in vitro and on animals highlighted vitamin K involvement in brain cells development and survival. In particular, vitamin K seems to have an antiapoptotic and anti-inflammatory effect mediated by the activation of Growth Arrest Specific Gene 6 and Protein S. Moreover, this vitamin is involved in sphingolipids metabolism, a class of lipids that participate in the proliferation, differentiation, and survival of brain cells. An altered expression in sphingolipids profile has been related to neuroinflammation and neurodegeneration. This review stems from a growing interest in the role of vitamin K in brain functions, especially in cognition, also in view of an expected increase of prevalence of Alzheimer's disease and other forms of dementia. It collects recent researches that show interesting, even though not definitive, evidence of a direct correlation between vitamin K levels and cognitive performance. Moreover, vitamin K antagonists, used worldwide as oral anticoagulants, according to recent studies may have a negative influence on cognitive domains such as visual memory, verbal fluency and brain volume. The aim of this review is to analyze the evidence of clinical studies carried out up to date on the relationship between vitamin K intake and cognitive performances. The involvement of vitamin K antagonists (VKAs) in declining cognitive performances is also addressed separately.
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BACKGROUND: Unilateral or bilateral metastases to extraocular muscles are very rare in breast cancer. CASE PRESENTATION: We describe a case of inferior rectus extraocular muscle involved by ductal luminal B/Her-2 neu negative breast cancer, observed in a cohort of 580 patients. Our patient had received chemotherapy and hormonal therapy (tamoxifen for 3 years and letrozole in the following 3 years) for her primary cancer and developed an orbital metastasis while she was under aromatase inhibitor-based therapy. Diagnosis was confirmed by MRI and biopsy. Orbital radiotherapy, combined with fulvestrant, resulted in shrinking of the secondary mass. A third line hormonal therapy using palbociclib was then started. Twelve-months later, MRI showed no residual tumor mass. Currently, the patient is alive and in good general conditions after 20 months. CONCLUSIONS: Literature review yielded 57 patients with extraocular muscle metastases from breast cancer, mostly due to the invasive lobular subtype of carcinoma. In addition to the present case, only 4 other extraocular muscles metastases from invasive ductal carcinoma has been reported, pointing out to the rarity of ductal type spread to the orbit in the natural history of breast cancer. Surgery may be used as a single treatment, despite no improvement of symptoms. Radiotherapy alone or combined with chemotherapy, or with chemotherapy plus hormonal therapy are available options. Results are, however, missing or poor. The present case is the first one with complete and stable response after 20 months to radiotherapy, antiestrogen drug fulvestrant and selective inhibitor of CDK4 /CDK6 palbociclib. In this subset of patients, with unusual metastatic sites and frequent multi-organ metastatic impairment, a multidisciplinary approach is indicated in order to achieve the best therapeutic management and long-term surveillance.