RESUMO
DEPDC5 is an upstream repressor of the mechanistic target of rapamycin pathway via the GATOR-1 complex. Pathogenic variants causing loss of function typically result in familial focal epilepsy with variable foci. Neuroimaging may either be normal or show brain malformations. Lesional and nonlesional cases may be present within the same family. Here, we describe a parent-child dyad affected by a truncating DEPDC5 pathogenic variant (c.727C > T; p.Arg243*), analyze the epilepsy clinical course, and describe neuroimaging characteristics from a 3T brain magnetic resonance imaging. Despite sharing the same variant, patients diverged both in terms of epilepsy severity and neuroimaging features. Surprisingly, the mother is still suffering from drug-resistant seizures and has normal neuroimaging, while the child has been experiencing prolonged seizure freedom notwithstanding a bottom-of-sulcus focal cortical dysplasia. An increasing gradient of severity has been proposed for families with GATOR1-related epilepsies. We confirm clinical and neuroradiological expressivities are variable and also suggest the prognostication of epilepsy outcome may be particularly difficult. The epilepsy outcome could partially be independent from brain structural abnormalities.
Assuntos
Epilepsia , Síndromes Epilépticas , Humanos , Progressão da Doença , Epilepsia/diagnóstico por imagem , Epilepsia/genética , Proteínas Ativadoras de GTPase/genética , Mutação , NeuroimagemRESUMO
Magnetic resonance fingerprinting (MRF) is highly promising as a quantitative MRI technique due to its accuracy, robustness, and efficiency. Previous studies have found high repeatability and reproducibility of 2D MRF acquisitions in the brain. Here, we have extended our investigations to 3D MRF acquisitions covering the whole brain using spiral projection k-space trajectories. Our travelling head study acquired test/retest data from the brains of 12 healthy volunteers and 8 MRI systems (3 systems at 3 T and 5 at 1.5 T, all from a single vendor), using a study design not requiring all subjects to be scanned at all sites. The pulse sequence and reconstruction algorithm were the same for all acquisitions. After registration of the MRF-derived PD T1 and T2 maps to an anatomical atlas, coefficients of variation (CVs) were computed to assess test/retest repeatability and inter-site reproducibility in each voxel, while a General Linear Model (GLM) was used to determine the voxel-wise variability between all confounders, which included test/retest, subject, field strength and site. Our analysis demonstrated a high repeatability (CVs 0.7-1.3% for T1, 2.0-7.8% for T2, 1.4-2.5% for normalized PD) and reproducibility (CVs of 2.0-5.8% for T1, 7.4-10.2% for T2, 5.2-9.2% for normalized PD) in gray and white matter. Both repeatability and reproducibility improved when compared to similar experiments using 2D acquisitions. Three-dimensional MRF obtains highly repeatable and reproducible estimations of T1 and T2, supporting the translation of MRF-based fast quantitative imaging into clinical applications.
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Encéfalo/diagnóstico por imagem , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética Multiparamétrica/métodos , Adulto , Feminino , Voluntários Saudáveis , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Reprodutibilidade dos TestesRESUMO
BACKGROUND: We compared protection of mycophenolate mofetil (MMF) and azathioprine (AZA) against acute cellular rejection (ACR) and chronic allograft nephropathy (CAN) in kidney transplant recipients on steroid-free, low-dose cyclosporine (CsA) microemulsion maintenance immunosuppression. METHODS AND FINDINGS: ATHENA, a pragmatic, prospective, multicenter trial conducted by 6 Italian transplant centers, compared the outcomes of 233 consenting recipients of a first deceased donor kidney transplant induced with low-dose thymoglobulin and basiliximab and randomized to MMF (750 mg twice/day, n = 119) or AZA (75 to 125 mg/day, n = 114) added-on maintenance low-dose CsA microemulsion and 1-week steroid. In patients without acute clinical or subclinical rejections, CsA dose was progressively halved. Primary endpoint was biopsy-proven CAN. Analysis was by intention to treat. Participants were included between June 2007 and July 2012 and followed up to August 2016. Between-group donor and recipient characteristics, donor/recipient mismatches, and follow-up CsA blood levels were similar. During a median (interquartile range (IQR)) follow-up of 47.7 (44.2 to 48.9) months, 29 of 87 biopsied patients on MMF (33.3%) versus 31 of 88 on AZA (35.2%) developed CAN (hazard ratio (HR) [95% confidence interval (CI)]: 1.147 (0.691 to 1.904, p = 0.595). Twenty and 21 patients on MMF versus 34 and 14 on AZA had clinical [HR (95% CI): 0.58 (0.34 to 1.02); p = 0.057) or biopsy-proven subclinical [HR (95% CI): 1.49 (0.76 to 2.92); p = 0.249] ACR, respectively. Combined events [HR (95% CI): 0.85 (0.56 to 1.29); p = 0.438], patient and graft survival, delayed graft function (DGF), 3-year glomerular filtration rate (GFR) [53.8 (40.6;65.7) versus 49.8 (36.8;62.5) mL/min/1.73 m2, p = 0.50], and adverse events (AEs) were not significantly different between groups. Chronicity scores other than CAN predict long-term graft outcome. Study limitations include small sample size and unblinded design. CONCLUSIONS: In this study, we found that in deceased donor kidney transplant recipients on low-dose CsA and no steroids, MMF had no significant benefits over AZA. This finding suggests that AZA, due to its lower costs, could safely replace MMF in combination with minimized immunosuppression. TRIAL REGISTRATION: ClinicalTrials.gov NCT00494741; EUDRACT 2006-005604-14.
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Azatioprina/administração & dosagem , Ciclosporina/administração & dosagem , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/administração & dosagem , Transplante de Rim , Ácido Micofenólico/administração & dosagem , Adulto , Idoso , Azatioprina/efeitos adversos , Ciclosporina/efeitos adversos , Quimioterapia Combinada , Feminino , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/imunologia , Humanos , Imunossupressores/efeitos adversos , Itália , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/efeitos adversos , Estudos Prospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
Polymicrogyria is a malformation of cortical folding and layering underlying different cognitive and neurological manifestations. The polymicrogyric cortex has heterogeneous morphofunctional patterns, qualitatively described at magnetic resonance imaging (MRI) by variable severity gradients and functional activations. We investigated the link between abnormal cortical folding and cortical function in order to improve surgical planning for patients with polymicrogyria and intractable epilepsy. We performed structural and functional MRI on 14 patients with perisylvian polymicrogyria and adopted surface-based methods to detect alterations of cortical thickness (CT) and local gyrification index (LGI) compared with normal cortex (30 age-matched subjects). We quantitatively assessed the grade of anatomic disruption of the polymicrogyric cortex and defined its relationship with decreased cortical function. We observed a good matching between visual analysis and morphometric measurements. CT maps revealed sparse clusters of thickening, while LGI maps disclosed circumscribed regions of maximal alteration with a uniformly decreasing centrifugal gradient. In polymicrogyric areas in which gyral and sulcal patterns were preserved, functional activation maintained the expected location, but was reduced in extent. Morphofunctional correlations, evaluated along cortico-cortical paths between maximum morphologic alterations and significant activations, identified an interindividual threshold for LGI (z-value = -1.09) beyond which functional activations were no longer identifiable.
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Mapeamento Encefálico , Polimicrogiria/diagnóstico por imagem , Polimicrogiria/fisiopatologia , Estudos de Casos e Controles , Feminino , Lateralidade Funcional , Humanos , Processamento de Imagem Assistida por Computador , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Oxigênio/sangueRESUMO
The current emphasis on kinetics and in situ control of molecular exchanges, across the tubular membrane, has not been paralleled by corresponding improvements in our understanding of tubular behaviour at the macroscopic level of classical physiology. In this paper, we propose a mathematical rationalization of macroscopic tubular transport by means of a principal transport equation, originating from the law of mass action between substrate and carrier. The other equations, derived from the main one, demonstrate the possibility of distinguishing between transporters with low affinity and high capacity and transporters with high affinity and low capacity. Moreover, our model formalizes both tubular reabsorption and tubular secretion. Regarding the renal calcium handling, our model confirms the two-compartment system proposed by Mioni in 1971, with some important variants, which are in agreement with the fractional reabsorptions of this cation along the tubule, as verified by micro-puncture technique. To obtain the frequency distribution of saturated tubules, we have utilized the infinitesimal analysis method, starting from the equations proposed by Smith in 1943, concluding that all titration curves result from the combined effect of enzymatic approach and anatomical heterogeneity of the nephrons. The theoretical equations included in our manuscript reflect substantial and palpable physiological mechanisms able to suggest diagnosis and therapy of some electrolyte and hormonal disorders. At the end of this paper, we highlight advantages and disadvantages detectable by comparing our mathematical approach with Marshall's and Bijvoet's methods, proposed, respectively, in 1976 and 1984.
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Glicosúria/fisiopatologia , Túbulos Renais/metabolismo , Reabsorção Renal/fisiologia , Equilíbrio Hidroeletrolítico/fisiologia , Animais , Calcifediol/sangue , Calcitriol/sangue , Cálcio/sangue , Cálcio/urina , Cães , Glicosúria/sangue , Glicosúria/urina , Humanos , Cinética , Computação Matemática , Hormônio Paratireóideo/sangue , Fenolsulfonaftaleína/metabolismo , Fosfatos/sangue , Fosfatos/urinaRESUMO
BACKGROUND: Kidney transplantation is the treatment of choice to restore fertility to women on renal replacement therapy. Over time, immunosuppressive, support therapies and approaches towards high-risk pregnancies have changed. The aim of this study was to analyse maternal-foetal outcomes in two cohorts of transplanted women who delivered a live-born baby in Italy in 1978-2013, dichotomized into delivery before and after January 2000. METHODS: A survey involving all the Italian transplant centres was carried out, gathering data on all pregnancies recorded since the start of activity at each centre; the estimated nationwide coverage was 75%. Data on cause of ESRD, dialysis, living/cadaveric transplantation, drug therapy, comorbidity, and the main maternal-foetal outcomes were recorded and reviewed. Data were compared with a low-risk cohort of pregnancies from two large Italian centres (2000-14; Torino and Cagliari Observational Study cohort). RESULTS: The database consists of 222 pregnancies with live-born babies after transplantation (83 before 2000 and 139 in 2000-13; 68 and 121 with baseline and birth data, respectively), and 1418 low-risk controls. The age of the patients significantly increased over time (1978-99: age 30.7 ± 3.7 versus 34.1 ± 3.7 in 2000-13; P < 0.001). Azathioprine, steroids and cyclosporine A were the main drugs employed in the first time period, while tacrolimus emerged in the second. The prevalence of early preterm babies increased from 13.4% in the first to 27.1% in the second period (P = 0.049), while late-preterm babies non-significantly decreased (38.8 versus 33.1%), thus leaving the prevalence of all preterm babies almost unchanged (52.2 and 60.2%; P = 0.372). Babies below the 5th percentile decreased over time (22.2 versus 9.6%; P = 0.036). In spite of high prematurity rates, no neonatal deaths occurred after 2000. The results in kidney transplant patients are significantly different from controls both considering all cases [preterm delivery: 57.3 versus 6.3%; early preterm: 22.2 versus 0.9%; small for gestational age (SGA): 14 versus 4.5%; P < 0.001] and considering only transplant patients with normal kidney function [preterm delivery: 35 versus 6.3%; early preterm: 10 versus 0.9%; SGA: 23.7 versus 4.5% (P < 0.001); risks increase across CKD stages]. Kidney function remained stable in most of the patients up to 6 months after delivery. Multiple regression analysis performed on the transplant cohort highlights a higher risk of preterm delivery in later CKD stages, an increase in preterm delivery and a decrease in SGA across periods. CONCLUSIONS: Pregnancy after transplantation has a higher risk of adverse outcomes compared with the general population. Over time, the incidence of SGA babies decreased while the incidence of 'early preterm' babies increased. Although acknowledging the differences in therapy (cyclosporine versus tacrolimus) and in maternal age (significantly increased), the decrease in SGA and the increase in prematurity may be explained by an obstetric policy favouring earlier delivery against the risk of foetal growth restriction.
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Imunossupressores/uso terapêutico , Transplante de Rim , Complicações na Gravidez , Nascimento Prematuro/epidemiologia , Sistema de Registros , Adulto , Feminino , Humanos , Incidência , Recém-Nascido , Itália/epidemiologia , Gravidez , Resultado da Gravidez , Inquéritos e QuestionáriosRESUMO
PURPOSE: To assess the capability of three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) sequences in detecting signal alterations of the endolabyrinthine fluid in patients with otosclerosis. MATERIALS AND METHODS: 3D-FLAIR before and after (-/+) gadolinium (Gd) administration was added to the standard MR protocol and acquired in 13 patients with a clinical/audiological diagnosis of severe/profound hearing loss in otosclerosis who were candidates for cochlear implantation and in 11 control subjects using 3-T magnetic resonance imaging (MRI) equipment. The MRI signal of the fluid-filled cochlea was assessed both visually and calculating the signal intensity ratio (SIR = signal intensity cochlea/brainstem). RESULTS: We revealed no endocochlear signal abnormalities on T1-weighted -/+ Gd images for either group, while on 3D-FLAIR we found bilateral hyperintensity with enhancement after Gd administration in eight patients and bilateral hyperintensity without enhancement in one patient. No endocochlear signal abnormalities were detected in other patients or the control group. CONCLUSION: Using 3-T MRI equipment, the 3D-FLAIR -/+ Gd sequence is able to detect the blood-labyrinth barrier (BLB) breakdown responsible for alterations of the endolabyrinthine fluid in patients with cochlear otosclerosis. We believe that 3D-FLAIR +/- Gd is an excellent imaging modality to assess the intra-cochlear damage in otosclerosis patients. KEY POINTS: ⢠Gd-enhanced T1-weighted MRI has limited application to detect intra-cochlear damage. ⢠3D-FLAIR is less sensitive to flux artefacts and allows multiplanar reconstruction. ⢠Post-Gd 3D-FLAIR is advantageous as it may highlight the BLB breakdown. ⢠Using 3D-FLAIR -/+ Gd, we were able to identify intra-cochlear signal hyperintensities. ⢠3D-FLAIR might be applied for monitoring disease progression and treatment response.
Assuntos
Otosclerose/diagnóstico por imagem , Adulto , Idoso , Artefatos , Estudos de Casos e Controles , Cóclea/diagnóstico por imagem , Implante Coclear , Meios de Contraste , Orelha Interna/diagnóstico por imagem , Feminino , Gadolínio , Gadolínio DTPA , Humanos , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Otosclerose/cirurgiaRESUMO
The approach to acid-base chemistry in medicine includes several methods. Currently, the two most popular procedures are derived from Stewart's studies and from the bicarbonate/BE-based classical formulation. Another method, unfortunately little known, follows the Kildeberg theory applied to acid-base titration. By using the data produced by Dana Atchley in 1933, regarding electrolytes and blood gas analysis applied to diabetes, we compared the three aforementioned methods, in order to highlight their strengths and their weaknesses. The results obtained, by reprocessing the data of Atchley, have shown that Kildeberg's approach, unlike the other two methods, is consistent, rational and complete for describing the organ-physiological behavior of the hydrogen ion turnover in human organism. In contrast, the data obtained using the Stewart approach and the bicarbonate-based classical formulation are misleading and fail to specify which organs or systems are involved in causing or maintaining the diabetic acidosis. Stewart's approach, despite being considered 'quantitative', does not propose in any way the concept of 'an amount of acid' and becomes even more confusing, because it is not clear how to distinguish between 'strong' and 'weak' ions. As for Stewart's approach, the classical method makes no distinction between hydrogen ions managed by the intermediate metabolism and hydroxyl ions handled by the kidney, but, at least, it is based on the concept of titration (base-excess) and indirectly defines the concept of 'an amount of acid'. In conclusion, only Kildeberg's approach offers a complete understanding of the causes and remedies against any type of acid-base disturbance.
Assuntos
Cetoacidose Diabética/sangue , Cetoacidose Diabética/urina , Eletrólitos , Rim/metabolismo , Prótons , Equilíbrio Ácido-Base , Bicarbonatos/sangue , Bicarbonatos/urina , Gasometria , Ácido Carbônico/sangue , Ácido Carbônico/urina , Cetoacidose Diabética/história , Cetoacidose Diabética/fisiopatologia , Eletrólitos/sangue , Eletrólitos/urina , História do Século XX , História do Século XXI , Humanos , Concentração de Íons de Hidrogênio , Hidróxidos/sangue , Hidróxidos/urina , Rim/fisiopatologiaRESUMO
SATB1 (MIM #602075) is a relatively new gene reported only in recent years in association with neurodevelopmental disorders characterized by variable facial dysmorphisms, global developmental delay, poor or absent speech, altered electroencephalogram (EEG), and brain abnormalities on imaging. To date about thirty variants in forty-four patients/children have been described, with a heterogeneous spectrum of clinical manifestations. In the present study, we describe a new patient affected by mild intellectual disability, speech disorder, and non-specific abnormalities on EEG and neuroimaging. Family studies identified a new de novo frameshift variant c.1818delG (p.(Gln606Hisfs*101)) in SATB1. To better define genotype-phenotype associations in the different types of reported SATB1 variants, we reviewed clinical data from our patient and from the literature and compared manifestations (epileptic activity, EEG abnormalities and abnormal brain imaging) due to missense variants versus those attributable to loss-of-function/premature termination variants. Our analyses showed that the latter variants are associated with less severe, non-specific clinical features when compared with the more severe phenotypes due to missense variants. These findings provide new insights into SATB1-related disorders.
Assuntos
Encéfalo , Eletroencefalografia , Epilepsia , Proteínas de Ligação à Região de Interação com a Matriz , Humanos , Proteínas de Ligação à Região de Interação com a Matriz/genética , Epilepsia/genética , Epilepsia/diagnóstico por imagem , Epilepsia/fisiopatologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/fisiopatologia , Masculino , Feminino , Mutação com Perda de Função , Deficiência Intelectual/genética , Deficiência Intelectual/diagnóstico por imagem , Deficiência Intelectual/patologia , Neuroimagem/métodos , Criança , Mutação da Fase de Leitura/genética , Fenótipo , Pré-EscolarRESUMO
Surgery for seizures arising from the rolandic area can be performed effectively, and accurate mapping of eloquent regions may improve seizure and functional outcome. Noninvasive cortical mapping is, however, hardly feasible in young children. We studied two children with epileptogenic focal cortical dysplasia (FCD) type IIb in the rolandic area, in whom preoperative passive task functional MRI (fMRI) during sedation helped planning a tailored surgical approach. In one patient the dysplastic cortex was functionally activated. After complete lesionectomy both children exhibited motor impairment that readily improved. Repeat fMRI, performed after complete (Patient 1) or partial (Patient 2) recovery, demonstrated relocation of motor-related activations posterior to the area of resection. fMRI during sedation can be used to demonstrate postsurgical functional reorganization of the motor cortex in young children. There is interindividual variability in functional activation of FCD type IIb.
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Encefalopatias/fisiopatologia , Epilepsia Rolândica/fisiopatologia , Neuroimagem Funcional/métodos , Imageamento por Ressonância Magnética/métodos , Malformações do Desenvolvimento Cortical/fisiopatologia , Encéfalo/fisiopatologia , Encefalopatias/cirurgia , Pré-Escolar , Epilepsia , Epilepsia Rolândica/cirurgia , Feminino , Humanos , Masculino , Malformações do Desenvolvimento Cortical/cirurgia , Malformações do Desenvolvimento Cortical do Grupo IRESUMO
Restless legs syndrome (RLS) is common in end-stage renal disease (ESRD) patients undergoing hemodialysis (HD). A few studies so far have investigated RLS prevalence in ESRD patients undergoing continuous ambulatory peritoneal dialysis (CAPD). The aim of this study was to compare the prevalence, characteristics, consequences and predictors of RLS between HD and CAPD patients. We recruited 58 HD and 28 CAPD patients. A neurologist expert in sleep medicine performed RLS diagnosis during a face-to-face interview. The prevalence of RLS was slightly higher in HD than in CAPD patients (19 vs. 10.7%). RLS appeared after the onset of kidney complaint in HD patients; in contrast, in CAPD patients RLS preceded the occurrence of renal disease. Five HD patients reported that RLS symptoms occurred throughout the dialysis session. HD patients with RLS(+) had a higher mean number of HD sessions per week and a longer mean duration of HD session than the RLS(-) ones. Prevalence of females was significantly higher in CAPD patients with RLS(+) than in the RLS(-) ones. RLS frequently affects both HD and CAPD patients. RLS impaired sleep in both groups, but use of dopaminergic agents was uncommon in our sample. Dialysis schedule was associated with RLS in HD patients, while female sex was related to RLS in CAPD patients. Awareness concerning RLS identification and treatment in HD and CAPD patients is recommended.
Assuntos
Falência Renal Crônica/epidemiologia , Falência Renal Crônica/terapia , Diálise Peritoneal Ambulatorial Contínua/efeitos adversos , Diálise Renal/efeitos adversos , Síndrome das Pernas Inquietas/diagnóstico , Síndrome das Pernas Inquietas/epidemiologia , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Falência Renal Crônica/sangue , Masculino , Pessoa de Meia-Idade , Síndrome das Pernas Inquietas/sangue , Fatores de Risco , Fatores Sexuais , Adulto JovemRESUMO
BACKGROUND: Disentangling physiological noise and signal of interest is a major issue when evaluating BOLD-signal changes in response to breath holding. Currently-adopted approaches for retrospective noise correction are general-purpose, and have non-negligible effects in studies on hypercapnic challenges. NEW METHOD: We provide a novel approach to the analysis of specific and non-specific BOLD-signal changes related to end-tidal CO2 (PETCO2) in breath-hold fMRI studies. Multiple-order nonlinear predictors for PETCO2 model a region-dependent nonlinear input-output relationship hypothesized in literature and possibly playing a crucial role in disentangling noise. We explore Retrospective Image-based Correction (RETROICOR) effects on the estimated BOLD response, applying our analysis both with and without RETROICOR and analyzing the linear and non-linear correlation between PETCO2 and RETROICOR regressors. RESULTS: The RETROICOR model of noise related to respiratory activity correlated with PETCO2 both linearly and non-linearly. The correction affected the shape of the estimated BOLD response to hypercapnia but allowed to discard spurious activity in ventricles and white matter. Activation clusters were best detected using non-linear components in the BOLD response model. COMPARISON WITH EXISTING METHOD: We evaluated the side-effects of standard physiological noise correction procedure, tailoring our analysis on challenging understudied brainstem and subcortical regions. Our novel approach allowed to characterize delays and non-linearities in BOLD response. CONCLUSIONS: RETROICOR successfully avoided false positives, still broadly affecting the estimated non-linear BOLD responses. Non-linearities in the model better explained CO2-related BOLD signal fluctuations. The necessity to modify the standard procedure for physiological-noise correction in breath-hold studies was addressed, stating its crucial importance.
Assuntos
Dióxido de Carbono , Substância Branca , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Tronco Encefálico , Suspensão da Respiração , Imageamento por Ressonância Magnética , Estudos RetrospectivosRESUMO
Friedreich's ataxia (FRDA) is an inherited neurodegenerative movement disorder with early onset, widespread cerebral and cerebellar pathology, and no cure still available. Functional MRI (fMRI) studies, although currently limited in number, have provided a better understanding of brain changes in people with FRDA. This systematic review aimed to provide a critical overview of the findings and methodologies of all fMRI studies conducted in genetically confirmed FRDA so far, and to offer recommendations for future study designs. About 12 cross-sectional and longitudinal fMRI studies, included 198 FRDA children and young adult patients and, 205 healthy controls (HCs), according to the inclusion criteria. Details regarding GAA triplet expansion and demographic and clinical severity measures were widely reported. fMRI designs included motor and cognitive task paradigms, and resting-state studies, with widespread changes in functionally activated areas and extensive variability in study methodologies. These studies highlight a mixed picture of both hypoactivation and hyperactivation in different cerebral and cerebellar brain regions depending on fMRI design and cohort characteristics. Functional changes often correlate with clinical variables. In aggregate, the findings provide support for cerebro-cerebellar loop damage and the compensatory mechanism hypothesis. Current literature indicates that fMRI is a valuable tool for gaining in vivo insights into FRDA pathology, but addressing that its limitations would be a key to improving the design, interpretation, and generalizability of studies in the future.
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PURPOSE: A prospective study was conducted to evaluate signal changes in the dentate nucleus, globus pallidus, pons, and thalamus (normalized to the deep cerebellum white matter) in T1-weighted magnetic resonance (MR) images after serial injections of gadobutrol in patients with thalassemia without neurological lesions. METHODS: In this study three groups were scanned at both 1.5â¯T and 3â¯T: 15 thalassemia patients transfused and chelated with ≥4 gadobutrol administrations at a high dose (0.2â¯mmol/kg per scan) for late gadolinium enhancement (LGE) cardiovascular MR, 8 thalassemia patients and 13 healthy subjects who had never received gadolinium-based contrast agents (GBCA). RESULTS: Signal intensity (SI) ratios at 1.5â¯T in all regions were comparable among the three groups and were not correlated with the number of gadobutrol administrations. In healthy subjects SI ratios were significantly different among the 4 regions, being higher in the pallidus. The SI ratios at 1.5â¯T were significantly higher and not correlated with SI ratios at 3â¯T or with iron overload in the same regions assessed by the T2* technique. CONCLUSION: This article describes the lack of increased SI in T1-weighted MR images after repeated administration of gadobutrol for cardiovascular MR studies in a high-risk population (high dose per scan, iron overload that can facilitate the transmetalation of gadolinium) scanned at 3â¯T and 1.5â¯T.
Assuntos
Meios de Contraste , Núcleos Cerebelares , Gadolínio , Gadolínio DTPA , Humanos , Espectroscopia de Ressonância Magnética , Compostos Organometálicos , Estudos Prospectivos , Estudos RetrospectivosRESUMO
Restless legs syndrome (RLS) is a possible consequence of end-stage renal disease. However, conclusive data on the association between RLS and chronic renal failure (CRF) in nondialyzed patients are still lacking. The aims of this study were: (1) to look for an association between RLS and CRF in nondialyzed patients; (2) to analyze the characteristics of RLS and its consequences on nocturnal rest in nondialyzed patients with CRF; (3) to identify possible predictors of RLS occurrence in nondialyzed patients with CRF. We recruited 138 nondialyzed patients with CRF (mean age: 69.8 +/- 11.7 years; male: 61.6%) and 151 controls (mean age: 60.2 +/- 18.6 years; male: 42.4%). An expert in sleep medicine investigated the presence of RLS by means of a face-to-face interview. Fifteen nondialyzed CRF patients and five controls were diagnosed as RLS affected. A multivariate analysis confirmed that RLS was independently associated with CRF in nondialyzed patients (P = 0.004). CRF patients RLS(+) were more commonly women and showed the presence of an iron deficiency compared with the RLS(-) ones. Independent predictors of RLS in nondialyzed CRF patients were: female sex (OR: 10.7, 95% CI: 2.2-31.3; P = 0.004) and percentage of transferrin saturation (OR: 0.6, 95% CI: 0.4-0.9; P = 0.04). This is the first case-control study able to recognize an association between RLS and CRF in patients not yet on dialysis. Nephrologists should investigate and treat RLS in their nondialyzed patients with CRF. In particular, physicians should carefully investigate women and patients with iron deficiency in the presence of RLS symptoms.
Assuntos
Falência Renal Crônica/complicações , Síndrome das Pernas Inquietas/etiologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome das Pernas Inquietas/diagnóstico , Estudos Retrospectivos , Índice de Gravidade de DoençaAssuntos
Inibidores de Calcineurina/efeitos adversos , Transplante de Coração , Imunossupressores/efeitos adversos , Falência Renal Crônica/cirurgia , Transplante de Rim , Complicações Pós-Operatórias/cirurgia , Idoso , Comorbidade , Reestenose Coronária/cirurgia , Feminino , Rejeição de Enxerto , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/cirurgia , Humanos , Falência Renal Crônica/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Complicações Pós-Operatórias/induzido quimicamente , Complicações Pós-Operatórias/etiologia , ReoperaçãoRESUMO
Magnetic resonance spectroscopy (MRS) is a non-invasive neuroimaging technique used to investigate in vivo brain metabolites. MRS could provide a sensitive tool for the study of hereditary spastic paraplegia (HSP) by helping to unveil the underlying biochemical mechanisms and monitoring response to treatment. This focused systematic review aimed to summarize the brain metabolite findings in studies performed in genetically determined HSP. The second aim was to provide a critical analysis and recommendations for well-designed protocols for future studies. Fourteen MRS studies have been analyzed with overall 61 HSP patients, falling within a wide range of age at onset, disease duration, and age at the MRS scan, including children and adults. The genetic diagnosis included several subtypes (SPG2/3/4/5/10/11/28/31/54). SPG11 and SPG54 have been more frequently investigated. The MRS methodology included different MR field strength, not easily comparable spectra areas varying from whole brain to various cortical areas, brain stem and cerebellum sampling. No consistency in disease severity and other outcome measures was observed. The main MRS findings corresponded to the white matter metabolite abnormalities in the corticospinal tracts. In summary, this focused review provides insights on the current knowledge of brain metabolites in HSP and, in particular, in SPG11 and SPG54. Despite the inhomogeneity of the studies to date reported, brain metabolites as assessed by MRS could represent potentially useful diagnostic markers and prognostic indicators of disease progression in HSP. Specific recommendations regarding the MRS technical protocol, CNS area sampling, study design, and applicability of findings are given.
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Hereditary spastic paraplegias (HSP) are a group of genetically and clinically heterogeneous neurologic disorders. Hereby we describe a relatively large group of patients (pts) affected by HSP studied at baseline (31 pts) and at follow-up (mean period 28.9 ± 8.4 months; 23 pts) with multimodal advanced MRI: high-resolution T1 images for voxel-based morphometry (VBM) analysis, magnetic resonance spectroscopy (MRS), and diffusion tensor imaging (DTI). An age-matched healthy control (HC) group underwent the same neuroimaging protocol in a time schedule matched with the HSP patients. At baseline, VBM showed gray matter (GM) reduction in HSP in the right pre-frontal cortex and bilaterally in the thalami. MRS at baseline depicted in HSP patients compared to the HC group reduction of NAA/Cr ratio in the right pre-frontal region, increase of Cho/Cr ratio in the right pre-central regions, and increase of mI/Cr ratio on the left pre-central area. At cross-sectional follow-up analysis and longitudinal evaluation, no VBM and MRS statistically significant results were obtained. Tract-based spatial statistics (TBSS) analysis showed widespread DTI brain white matter (WM) alterations in patients compared to HC at baseline, which are characterized by reduction of fractional anisotropy (FA) and increase of mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity, as confirmed on cross-analysis of the follow-up dataset. A longitudinal analysis with TBSS in HSP patients did not show significant variations, while upon applying region-based analysis we found increased FA and decreased MD and AD in specific brain WM fiber complex during follow-up. The changes were not correlated with the clinical presentation (pure vs complicated HSP), motor function, and motility indexes or history of specific treatments (botulinum toxin). In conclusion, the cross-sectional analysis of the multiparametric MRI data in our HSP patients confirmed the non-prominent involvement of the cortex in the primary motor regions but rather of other more associative areas. On the contrary, DTI demonstrated a widespread involvement of the brain WM, including the primary motor regions, which was confirmed at follow-up. The longitudinal analysis revealed an apparent inversion of tendency when considering the expected evolution of a neurodegenerative process: we detected an increase of FA and a decrease of MD and AD. These time-related modifications may suggest a repair attempt by the residual central WM fibers, which requires confirmation with a larger group of patients and with a longer time interval.
RESUMO
Mapping brain functions is crucial for neurosurgical planning in patients with drug-resistant seizures. However, presurgical language mapping using either functional or structural networks can be challenging, especially in children. In fact, most of the evidence on this topic derives from cross-sectional or retrospective studies in adults submitted to anterior temporal lobectomy. In this prospective study, we used fMRI and DTI to explore patterns of language representation, their predictors and impact on cognitive performances in 29 children and young adults (mean age at surgery: 14.6 ± 4.5 years) with focal lesional epilepsy. In 20 of them, we also assessed the influence of epilepsy surgery on language lateralization. All patients were consecutively enrolled at a single epilepsy surgery center between 2009 and 2015 and assessed with preoperative structural and functional 3T brain MRI during three language tasks: Word Generation (WG), Rhyme Generation (RG) and a comprehension task. We also acquired DTI data on arcuate fasciculus in 24 patients. We first assessed patterns of language representation (relationship of activations with the epileptogenic lesion and Laterality Index (LI)) and then hypothesized a causal model to test whether selected clinical variables would influence the patterns of language representation and the ensuing impact of the latter on cognitive performances. Twenty out of 29 patients also underwent postoperative language fMRI. We analyzed possible changes of fMRI and DTI LIs and their clinical predictors. Preoperatively, we found atypical language lateralization in four patients during WG task, in one patient during RG task and in seven patients during the comprehension task. Diffuse interictal EEG abnormalities predicted a more atypical language representation on fMRI (p = 0.012), which in turn correlated with lower attention (p = 0.036) and IQ/GDQ scores (p = 0.014). Postoperative language reorganization implied shifting towards atypical language representation. Abnormal postoperative EEG (p = 0.003) and surgical failures (p = 0.015) were associated with more atypical language lateralization, in turn correlating with worsened fluency. Neither preoperative asymmetry nor postoperative DTI LI changes in the arcuate fasciculus were observed. Focal lesional epilepsy associated with diffuse EEG abnormalities may favor atypical language lateralization and worse cognitive performances, which are potentially reversible after successful surgery.
Assuntos
Mapeamento Encefálico , Epilepsias Parciais/diagnóstico por imagem , Epilepsias Parciais/psicologia , Transtornos da Linguagem/diagnóstico por imagem , Transtornos da Linguagem/psicologia , Adolescente , Criança , Cognição , Compreensão , Imagem de Tensor de Difusão , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/psicologia , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsias Parciais/cirurgia , Feminino , Lateralidade Funcional , Neuroimagem Funcional , Humanos , Imageamento por Ressonância Magnética , Masculino , Estudos Prospectivos , Adulto JovemRESUMO
Biological visual systems are extraordinarily capable of recovering the shape and brightness of objects from sparse and fragmentary information. Using functional magnetic imaging, we show that two associative areas of the dorsal pathway--in the caudal region of the intrapariatal sulcus and in the lateral occipital sulcus--respond specifically to the Craik-O'Brien-Cornsweet illusion generated by high-pass filtered edges. Other visual areas, including primary visual cortex, also respond strongly to the retinotopic location of the edge, but these areas respond equally well to a line of matched contrast and detectability, rather than specifically to the brightness illusion. The reconstruction of surface and/or its brightness seems to be achieved by associative areas from the information about visual features provided by the primary visual cortices, even where there is no physical difference in luminance.