RESUMO
BACKGROUND: Iron content is increased in the substantia nigra of persons with Parkinson's disease and may contribute to the pathophysiology of the disorder. Early research suggests that the iron chelator deferiprone can reduce nigrostriatal iron content in persons with Parkinson's disease, but its effects on disease progression are unclear. METHODS: We conducted a multicenter, phase 2, randomized, double-blind trial involving participants with newly diagnosed Parkinson's disease who had never received levodopa. Participants were assigned (in a 1:1 ratio) to receive oral deferiprone at a dose of 15 mg per kilogram of body weight twice daily or matched placebo for 36 weeks. Dopaminergic therapy was withheld unless deemed necessary for symptom control. The primary outcome was the change in the total score on the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS; range, 0 to 260, with higher scores indicating more severe impairment) at 36 weeks. Secondary and exploratory clinical outcomes at up to 40 weeks included measures of motor and nonmotor disability. Brain iron content measured with the use of magnetic resonance imaging was also an exploratory outcome. RESULTS: A total of 372 participants were enrolled; 186 were assigned to receive deferiprone and 186 to receive placebo. Progression of symptoms led to the initiation of dopaminergic therapy in 22.0% of the participants in the deferiprone group and 2.7% of those in the placebo group. The mean MDS-UPDRS total score at baseline was 34.3 in the deferiprone group and 33.2 in the placebo group and increased (worsened) by 15.6 points and 6.3 points, respectively (difference, 9.3 points; 95% confidence interval, 6.3 to 12.2; P<0.001). Nigrostriatal iron content decreased more in the deferiprone group than in the placebo group. The main serious adverse events with deferiprone were agranulocytosis in 2 participants and neutropenia in 3 participants. CONCLUSIONS: In participants with early Parkinson's disease who had never received levodopa and in whom treatment with dopaminergic medications was not planned, deferiprone was associated with worse scores in measures of parkinsonism than those with placebo over a period of 36 weeks. (Funded by the European Union Horizon 2020 program; FAIRPARK-II ClinicalTrials.gov number, NCT02655315.).
Assuntos
Antiparkinsonianos , Deferiprona , Quelantes de Ferro , Ferro , Doença de Parkinson , Substância Negra , Humanos , Deferiprona/administração & dosagem , Deferiprona/efeitos adversos , Deferiprona/farmacologia , Deferiprona/uso terapêutico , Ferro/análise , Ferro/metabolismo , Levodopa/uso terapêutico , Neutropenia/induzido quimicamente , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Doença de Parkinson/fisiopatologia , Quelantes de Ferro/administração & dosagem , Quelantes de Ferro/efeitos adversos , Quelantes de Ferro/farmacologia , Quelantes de Ferro/uso terapêutico , Substância Negra/química , Substância Negra/diagnóstico por imagem , Substância Negra/efeitos dos fármacos , Substância Negra/metabolismo , Progressão da Doença , Método Duplo-Cego , Administração Oral , Encéfalo/diagnóstico por imagem , Química Encefálica , Dopaminérgicos/administração & dosagem , Dopaminérgicos/efeitos adversos , Dopaminérgicos/farmacologia , Dopaminérgicos/uso terapêutico , Antiparkinsonianos/administração & dosagem , Antiparkinsonianos/efeitos adversos , Antiparkinsonianos/farmacologia , Antiparkinsonianos/uso terapêuticoRESUMO
Caffeine consumption outcomes on Amyotrophic Lateral Sclerosis (ALS) including progression, survival and cognition remain poorly defined and may depend on its metabolization influenced by genetic variants. 378 ALS patients with a precise evaluation of their regular caffeine consumption were monitored as part of a prospective multicenter study. Demographic, clinical characteristics, functional disability as measured with revised ALS Functional Rating Scale (ALSFRS-R), cognitive deficits measured using Edinburgh Cognitive and Behavioural ALS Screen (ECAS), survival and riluzole treatment were recorded. 282 patients were genotyped for six single nucleotide polymorphisms tagging different genes involved in caffeine intake and/or metabolism: CYP1A1 (rs2472297), CYP1A2 (rs762551), AHR (rs4410790), POR (rs17685), XDH (rs206860) and ADORA2A (rs5751876) genes. Association between caffeine consumption and ALSFRS-R, ALSFRS-R rate, ECAS and survival were statistically analyzed to determine the outcome of regular caffeine consumption on ALS disease progression and cognition. No association was observed between caffeine consumption and survival (p = 0.25), functional disability (ALSFRS-R; p = 0.27) or progression of ALS (p = 0.076). However, a significant association was found with higher caffeine consumption and better cognitive performance on ECAS scores in patients carrying the C/T and T/T genotypes at rs2472297 (p-het = 0.004). Our results support the safety of regular caffeine consumption on ALS disease progression and survival and also show its beneficial impact on cognitive performance in patients carrying the minor allele T of rs2472297, considered as fast metabolizers, that would set the ground for a new pharmacogenetic therapeutic strategy.
Assuntos
Esclerose Lateral Amiotrófica , Cafeína , Citocromo P-450 CYP1A2 , Progressão da Doença , Polimorfismo de Nucleotídeo Único , Receptor A2A de Adenosina , Humanos , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/tratamento farmacológico , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Receptor A2A de Adenosina/genética , Citocromo P-450 CYP1A2/genética , Cognição/fisiologia , Cognição/efeitos dos fármacos , Estudos Prospectivos , Citocromo P-450 CYP1A1/genética , Receptores de Hidrocarboneto Arílico/genética , Adulto , Disfunção Cognitiva/genética , Riluzol/uso terapêutico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Fatores de Transcrição Hélice-Alça-Hélice BásicosRESUMO
BACKGROUND: The choice between different diffusion-weighted imaging (DWI) techniques is difficult as each comes with tradeoffs for efficient clinical routine imaging and apparent diffusion coefficient (ADC) accuracy. PURPOSE: To quantify signal-to-noise-ratio (SNR) efficiency, ADC accuracy, artifacts, and distortions for different DWI acquisition techniques, coils, and scanners. STUDY TYPE: Phantom, in vivo intraindividual biomarker accuracy between DWI techniques and independent ratings. POPULATION/PHANTOMS: NIST diffusion phantom. 51 Patients: 40 with prostate cancer and 11 with head-and-neck cancer at 1.5 T FIELD STRENGTH/SEQUENCE: Echo planar imaging (EPI): 1.5 T and 3 T Siemens; 3 T Philips. Distortion-reducing: RESOLVE (1.5 and 3 T Siemens); Turbo Spin Echo (TSE)-SPLICE (3 T Philips). Small field-of-view (FOV): ZoomitPro (1.5 T Siemens); IRIS (3 T Philips). Head-and-neck and flexible coils. ASSESSMENT: SNR Efficiency, geometrical distortions, and susceptibility artifacts were quantified for different b-values in a phantom. ADC accuracy/agreement was quantified in phantom and for 51 patients. In vivo image quality was independently rated by four experts. STATISTICAL TESTS: QIBA methodology for accuracy: trueness, repeatability, reproducibility, Bland-Altman 95% Limits-of-Agreement (LOA) for ADC. Wilcoxon Signed-Rank and student tests on P < 0.05 level. RESULTS: The ZoomitPro small FOV sequence improved b-image efficiency by 8%-14%, reduced artifacts and observer scoring for most raters at the cost of smaller FOV compared to EPI. The TSE-SPLICE technique reduced artifacts almost completely at a 24% efficiency cost compared to EPI for b-values ≤500 sec/mm2 . Phantom ADC 95% LOA trueness were within ±0.03 × 10-3 mm2 /sec except for small FOV IRIS. The in vivo ADC agreement between techniques, however, resulted in 95% LOAs in the order of ±0.3 × 10-3 mm2 /sec with up to 0.2 × 10-3 mm2 /sec of bias. DATA CONCLUSION: ZoomitPro for Siemens and TSE SPLICE for Philips resulted in a trade-off between efficiency and artifacts. Phantom ADC quality control largely underestimated in vivo accuracy: significant ADC bias and variability was found between techniques in vivo. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.
Assuntos
Cabeça , Pescoço , Masculino , Humanos , Reprodutibilidade dos Testes , Imagens de Fantasmas , Imagem de Difusão por Ressonância Magnética/métodos , Imagem Ecoplanar/métodosRESUMO
BACKGROUND: The objective of breast reconstruction (BR) is to erase the after-effects of total mastectomy by allowing patients to restore their breast shape. The aim of our study was to investigate the body map integration of different types of BR using functional magnetic resonance (fMRI). PATIENTS AND METHODS: We prospectively enrolled all women undergoing BR for breast cancer to the Remasco study (NCT02553967). Participants were categorized into four groups according to the standard of care they required: immediate BR (IBR), delayed BR (DBR), flap (autologous), or implant BR. Each patient performed sensorimotor tasks during the fMRI acquisition. RESULTS: Data of 38 patients were analyzed. We identified the cingulate region as the area of interest in the brain. In the case of DBR, the brain area activated during palpation of the total mastectomy scar (before BR) was different from the brain area activated during palpation of the reconstructed breast (Brodmann areas 31 versus 32). Palpation of the native breast and reconstructed breast activated the same Brodmann area 32. Comparing the brain activation signal during palpation of the native breast and the reconstructed breast did not reveal any significant difference in the overall population (P = 0.41) or in the groups: autologous (P = 0.32), implant (P = 0.10), IBR (P = 0.72), or DBR (P = 0.10). CONCLUSIONS: This experimental study allowed us to describe and understand the brain plasticity processes that accompany BR. The results suggest that the reconstructed breast is integrated into the body schema, regardless of the type of BR or the timing.
Assuntos
Neoplasias da Mama , Mamoplastia , Imagem Corporal , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Feminino , Humanos , Imageamento por Ressonância Magnética , Mamoplastia/métodos , MastectomiaRESUMO
BACKGROUND: The "dual syndrome hypothesis" distinguished two subtypes in mild cognitive impairment (MCI) in Parkinson's disease: frontostriatal, characterized by attentional and executive deficits; and posterior cortical, characterized by visuospatial, memory, and language deficits. OBJECTIVE: The aim was to identify resting-state functional modifications associated with these subtypes. METHODS: Ninety-five nondemented patients categorized as having normal cognition (n = 31), frontostriatal (n = 14), posterior cortical (n = 20), or mixed (n = 30) cognitive subtype had a 3 T resting-state functional magnetic resonance imaging scan. Twenty-four age-matched healthy controls (HCs) were also included. A group-level independent component analysis was performed to identify resting-state networks, and the selected components were subdivided into 564 cortical regions in addition to 26 basal ganglia regions. Global intra- and inter-network connectivity along with global and local efficiencies was compared between groups. The network-based statistics approach was used to identify connections significantly different between groups. RESULTS: Patients with posterior cortical deficits had increased intra-network functional connectivity (FC) within the basal ganglia network compared with patients with frontostriatal deficits. Patients with frontostriatal deficits had reduced inter-network FC between several networks, including the visual, default-mode, sensorimotor, salience, dorsal attentional, basal ganglia, and frontoparietal networks, compared with HCs, patients with normal cognition, and patients with a posterior cortical subtype. Similar results were also found between patients with a mixed subtype and HCs. CONCLUSION: MCI subtypes are associated with specific changes in resting-state FC. Longitudinal studies are needed to determine the predictive potential of these markers regarding the risk of developing dementia. © 2021 International Parkinson and Movement Disorder Society.
Assuntos
Disfunção Cognitiva , Doença de Parkinson , Encéfalo/patologia , Mapeamento Encefálico , Disfunção Cognitiva/complicações , Disfunção Cognitiva/etiologia , Humanos , Imageamento por Ressonância Magnética , Testes Neuropsicológicos , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/patologiaRESUMO
The posterior parietal cortex (PPC) is a key structure for visual attention and upper limb function, two features that could be impaired after stroke, and could be implied in their recovery. If it is well established that stroke is responsible for intra- and interhemispheric connectivity troubles, little is known about those existing for the contralesional PPC. In this study, we aimed at mapping the functional (using resting state fMRI) and structural (using diffusion tensor imagery) networks from 3 subparts of the PPC of the contralesional hemisphere (the anterior intraparietal sulcus), the posterior intraparietal sulcus and the superior parieto-occipital cortex to bilateral frontal areas and ipsilesional homologous PPC parts in 11 chronic stroke patients compared to 13 healthy controls. We also aimed at assessing the relationship between connectivity and the severity of visuospatial and motor deficiencies. We showed that interhemispheric functional and structural connectivity between PPCs was altered in stroke patients compared to controls, without any specificity among seeds. Alterations of parieto-frontal intra- and interhemispheric connectivity were less observed. Neglect severity was associated with several alterations in intra- and interhemispheric connectivity, whereas we did not find any behavioral/connectivity correlations for motor deficiency. The results of this exploratory study shed a new light on the influence of the contralesional PPC in post-stroke patients, they have to be confirmed and refined in further larger studies.
Assuntos
Transtornos Motores/fisiopatologia , Lobo Parietal/patologia , Lobo Parietal/fisiopatologia , Transtornos da Percepção/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Atenção , Imagem de Tensor de Difusão , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Lobo Occipital/fisiopatologiaRESUMO
The optic radiations (OR) are white matter tracts forming the posterior part of the visual ways. As an important inter-individual variability exists, atlases may be inefficient to locate the OR in a given subject. We designed a fully automatic method to delimitate the OR on a magnetic resonance imaging using tractography. On 15 healthy subjects, we evaluated the validity of our method by comparing the outputs to the Jülich post-mortem histological atlas, and its reproducibility. We also evaluated its feasibility on 98 multiple sclerosis (MS) patients. We correlated different visual outcomes with the inflammatory lesions volume within the OR reconstructed with different methods (our method, atlas, TractSeg). Our method reconstructed the OR bundle in all healthy subjects (< 2 h for most of them), and was reproducible. It demonstrated good classification indexes: sensitivity up to 0.996, specificity up to 0.993, Dice coefficient up to 0.842, and an area under the receiver operating characteristic (ROC) curve of 0.981. Our method reconstructed the OR in 91 of the 98 MS patients (92.9%, < 6 h for most of patients). Compared to an atlas-based approach and the TractSeg method, the inflammatory lesions volume in the OR measured with our method better correlated with the visual cortex volume, visual acuity and mean peripapillar retinal nerve fiber layer thickness. Our method seems to be efficient to reconstruct the OR in healthy subjects, and seems applicable to MS patients. It may be more relevant than an atlas based approach.
Assuntos
Esclerose Múltipla , Vias Visuais , Automação , Humanos , Esclerose Múltipla/diagnóstico por imagem , Fibras Nervosas , Reprodutibilidade dos Testes , Vias Visuais/diagnóstico por imagemRESUMO
OBJECTIVES: Early-onset Alzheimer's disease (EOAD) begins before the age of 65 and is characterized by a faster clinical course and the frequency of nonamnestic symptoms compared to late onset Alzheimer disease (LOAD). However, the pathophysiological process of EOAD remains unclear. We expected that ASL may show widespread cortical hypoperfusion in EOAD compared to LOAD and in nonamnestic EOAD compared to amnestic EOAD. METHODS: In this study, 26 EOAD patients (16 amnestic and 10 nonamnestic patients), 29 LOAD patients and 12 healthy controls underwent pseudo-continuous ASL and 3D FFE T1 sequences. Statistical comparisons between EOAD, LOAD and control groups were made after surface-based analysis of CBF maps in regressing out the cortical thickness. RESULTS: ASL showed a more severe hypoperfusion in nonamnestic EOAD patients compared to amnestic EOAD ones, with mean CBF values (± std) of 26.9 (± 3.8) and 46.6 (± 24.1) mL/100 g/min respectively (P = 0.014), located in the bilateral temporo-parietal neocortex, the precuneus, the posterior cingulate cortices (PCC) and frontal lobes. Comparison between EOAD and LOAD patients showed a trend to hypoperfusion in the left parietal lobe, PCC and precuneus in EOAD (P < 0.001 uncorrected). CONCLUSIONS: Different patterns of hypoperfusion between nonamnestic and amnestic EOAD subtypes were identified, with a more severe and extensive hypoperfusion in nonamnestic patients. A trend towards more severe hypoperfusion was detected in EOAD compared to LOAD. Further studies are needed to validate ASL as a potential tool for the distinction of EOAD subtypes and the prediction of the time course of the disease.
Assuntos
Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/fisiopatologia , Amnésia/diagnóstico por imagem , Amnésia/fisiopatologia , Encéfalo/irrigação sanguínea , Encéfalo/fisiopatologia , Idoso , Doença de Alzheimer/complicações , Amnésia/complicações , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Marcadores de SpinRESUMO
PURPOSE: Medial lobe temporal structures and more specifically the hippocampus play a decisive role in episodic memory. Most of the memory functional magnetic resonance imaging (fMRI) studies evaluate the encoding phase; the retrieval phase being performed outside the MRI. We aimed to determine the ability to reveal greater hippocampal fMRI activations during retrieval phase. MATERIALS AND METHODS: Thirty-five epileptic patients underwent a two-step memory fMRI. During encoding phase, subjects were requested to identify the feminine or masculine gender of faces and words presented, in order to encourage stimulus encoding. One hour after, during retrieval phase, subjects had to recognize the word and face. We used an event-related design to identify hippocampal activations. RESULTS: There was no significant difference between patients with left temporal lobe epilepsy, patients with right temporal lobe epilepsy and patients with extratemporal lobe epilepsy on verbal and visual learning task. For words, patients demonstrated significantly more bilateral hippocampal activation for retrieval task than encoding task and when the tasks were associated than during encoding alone. Significant difference was seen between face-encoding alone and face retrieval alone. CONCLUSIONS: This study demonstrates the essential contribution of the retrieval task during a fMRI memory task but the number of patients with hippocampal activations was greater when the two tasks were taken into account.
Assuntos
Epilepsia/fisiopatologia , Epilepsia/psicologia , Hipocampo/fisiopatologia , Rememoração Mental/fisiologia , Adulto , Idoso , Mapeamento Encefálico , Epilepsia/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Adulto JovemRESUMO
BACKGROUND: Postnatal adaptation requires liquid clearance and lung aeration. However, their relative contribution to the expansion of functional residual capacity (FRC) has not been fully investigated. We studied evolution of lung liquid removal and lung aeration after birth in preterm lambs. METHODS: Lung liquid content and lung volume were assessed at birth and every 30 min over 2 h using magnetic resonance imaging (MRI) in three groups of lambs delivered by cesarean: preterm, late preterm, and late preterm with antenatal steroids. Lung function and mechanics of the respiratory system were also measured. RESULTS: Lung liquid content increased by approximately 30% in the preterm group (P < 0.05), whereas it did not change significantly in the late preterm lambs. Antenatal steroids induced a 50% drop in the lung liquid content (P < 0.05). Total lung volume increased in all groups (P < 0.05) but was higher in the late preterm + steroids group relative to other groups (P < 0.05). Compliance and resistances of the respiratory system were significantly correlated with lung liquid content (P < 0.05). CONCLUSION: FRC expansion results mainly from an increase in lung volume rather than a decrease in lung liquid in preterm and late preterm lambs. Antenatal steroids promote FRC expansion through increases in lung volume and liquid clearance.
Assuntos
Capacidade Residual Funcional , Pulmão/diagnóstico por imagem , Pulmão/fisiologia , Animais , Animais Recém-Nascidos , Peso ao Nascer , Complacência Pulmonar , Imageamento por Ressonância Magnética , Nascimento Prematuro , Respiração , Testes de Função Respiratória , Ovinos , Carneiro Doméstico , Volume de Ventilação Pulmonar , Fatores de TempoRESUMO
Stereotactic radiosurgery (SRS) is the accurate, conformal delivery of high-dose radiation to well-defined targets while minimizing normal structure doses via steep dose gradients. While inverse treatment planning (ITP) with computerized optimization algorithms are routine, many aspects of the planning process remain user-dependent. We performed an international, multi-institutional benchmark trial to study planning variability and to analyze preferable ITP practice for spinal robotic radiosurgery. 10 SRS treatment plans were generated for a complex-shaped spinal metastasis with 21 Gy in 3 fractions and tight constraints for spinal cord (V14Gy < 2 cc, V18Gy < 0.1 cc) and target (coverage > 95%). The resulting plans were rated on a scale from 1 to 4 (excellent-poor) in five categories (constraint compliance, optimization goals, low-dose regions, ITP complexity, and clinical acceptability) by a blinded review panel. Additionally, the plans were mathemati-cally rated based on plan indices (critical structure and target doses, conformity, monitor units, normal tissue complication probability, and treatment time) and compared to the human rankings. The treatment plans and the reviewers' rankings varied substantially among the participating centers. The average mean overall rank was 2.4 (1.2-4.0) and 8/10 plans were rated excellent in at least one category by at least one reviewer. The mathematical rankings agreed with the mean overall human rankings in 9/10 cases pointing toward the possibility for sole mathematical plan quality comparison. The final rankings revealed that a plan with a well-balanced trade-off among all planning objectives was preferred for treatment by most par-ticipants, reviewers, and the mathematical ranking system. Furthermore, this plan was generated with simple planning techniques. Our multi-institutional planning study found wide variability in ITP approaches for spinal robotic radiosurgery. The participants', reviewers', and mathematical match on preferable treatment plans and ITP techniques indicate that agreement on treatment planning and plan quality can be reached for spinal robotic radiosurgery.
Assuntos
Radiocirurgia/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Robótica/métodos , Neoplasias da Coluna Vertebral/cirurgia , Algoritmos , Benchmarking , Humanos , Agências Internacionais , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodosRESUMO
The purpose of this study was to demonstrate that Monte Carlo treatment planning systems require tissue characterization (density and composition) as a function of CT number. A discrete set of tissue classes with a specific composition is introduced. In the current work we demonstrate that, for megavoltage photon radiotherapy, only the hydrogen content of the different tissues is of interest. This conclusion might have an impact on MRI-based dose calculations and on MVCT calibration using tissue substitutes. A stoichiometric calibration was performed, grouping tissues with similar atomic composition into 15 dosimetrically equivalent subsets. To demonstrate the importance of hydrogen, a new scheme was derived, with correct hydrogen content, complemented by oxygen (all elements differing from hydrogen are replaced by oxygen). Mass attenuation coefficients and mass stopping powers for this scheme were calculated and compared to the original scheme. Twenty-five CyberKnife treatment plans were recalculated by an in-house developed Monte Carlo system using tissue density and hydrogen content derived from the CT images. The results were compared to Monte Carlo simulations using the original stoichiometric calibration. Between 300 keV and 3 MeV, the relative difference of mass attenuation coefficients is under 1% within all subsets. Between 10 keV and 20 MeV, the relative difference of mass stopping powers goes up to 5% in hard bone and remains below 2% for all other tissue subsets. Dose-volume histograms (DVHs) of the treatment plans present no visual difference between the two schemes. Relative differences of dose indexes D98, D95, D50, D05, D02, and Dmean were analyzed and a distribution centered around zero and of standard deviation below 2% (3 σ) was established. On the other hand, once the hydrogen content is slightly modified, important dose differences are obtained. Monte Carlo dose planning in the field of megavoltage photon radiotherapy is fully achievable using only hydrogen content of tissues, a conclusion that might impact MRI dose calculation, but can also help selecting the optimal tissue substitutes when calibrating MVCT devices.
Assuntos
Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/radioterapia , Hidrogênio/metabolismo , Método de Monte Carlo , Fótons/uso terapêutico , Planejamento da Radioterapia Assistida por Computador/métodos , Algoritmos , Neoplasias Ósseas/secundário , Calibragem , Seguimentos , Humanos , Radiometria , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada , Estudos Retrospectivos , Distribuição Tecidual , Tomografia Computadorizada por Raios X/métodosRESUMO
A dosimetric comparison was made of Helical Tomotherapy (HT) and Rapid'Arc(®) (RA) in 115 patients with head and neck carcinoma included in a prospective and multicentric study. HT and RA provided highly conformal plans that easily complied with dose volume constraints for organs at risk. HT reduced high doses to the planning target volumes (PTVs) compared to RA and provided a more homogeneous dose distribution but with an increased Non Tumoral Integral Dose (NTID) than RA. However, the clinical consequences of these dosimetric advantages and disadvantages need further investigation.
Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Radiometria/métodos , Radioterapia de Intensidade Modulada/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Radiometria/efeitos adversos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada/efeitos adversos , Adulto JovemRESUMO
BACKGROUND: Anxiety in Parkinson's disease (PD) has been associated with grey matter changes and functional changes in anxiety-related neuronal circuits. So far, no study has analyzed white matter (WM) changes in patients with PD and anxiety. OBJECTIVE: The aim of this study was to identify WM changes by comparing PD patients with and without anxiety, using diffusion-tensor imaging (DTI). METHODS: 108 non-demented PD patients with (nâ=â31) and without (nâ=â77) anxiety as defined by their score on the Parkinson Anxiety Scale participated. DTI was used to determine the fractional anisotropy (FA) and mean diffusivity (MD) in specific tracts within anxiety-related neuronal circuits. Mean FA and MD were compared between groups and correlated with the severity of anxiety adjusted by sex, center, Hoehn & Yahr stage, levodopa equivalent daily dosage, and Hamilton depression rating scale. RESULTS: Compared to patients without anxiety, PD patients with anxiety showed lower FA within the striato-orbitofrontal, striato-cingulate, cingulate-limbic, and caudate-thalamic tracts; higher FA within the striato-limbic and accumbens-thalamic tracts; higher MD within the striato-thalamic tract and lower MD within the striato-limbic tract. CONCLUSIONS: Anxiety in PD is associated with microstructural alterations in anxiety-related neuronal circuits within the WM. This result reinforces the view that PD-related anxiety is linked to structural alteration within the anxiety-related brain circuits.
Assuntos
Doença de Parkinson , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Ansiedade/diagnóstico por imagem , Ansiedade/etiologia , Encéfalo/diagnóstico por imagem , Substância Cinzenta , LevodopaRESUMO
BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common reproductive-endocrine disorder affecting between 5 and 18% of women worldwide. An elevated frequency of pulsatile luteinizing hormone (LH) secretion and higher serum levels of anti-Müllerian hormone (AMH) are frequently observed in women with PCOS. The origin of these abnormalities is, however, not well understood. METHODS: We studied brain structure and function in women with and without PCOS using proton magnetic resonance spectroscopy (MRS) and diffusion tensor imaging combined with fiber tractography. Then, using a mouse model of PCOS, we investigated by electron microscopy whether AMH played a role on the regulation of hypothalamic structural plasticity. FINDINGS: Increased AMH serum levels are associated with increased hypothalamic activity/axonal-glial signalling in PCOS patients. Furthermore, we demonstrate that AMH promotes profound micro-structural changes in the murine hypothalamic median eminence (ME), creating a permissive environment for GnRH secretion. These include the retraction of the processes of specialized AMH-sensitive ependymo-glial cells called tanycytes, allowing more GnRH neuron terminals to approach ME blood capillaries both during the run-up to ovulation and in a mouse model of PCOS. INTERPRETATION: We uncovered a central function for AMH in the regulation of fertility by remodeling GnRH terminals and their tanycytic sheaths, and provided insights into the pivotal role of the brain in the establishment and maintenance of neuroendocrine dysfunction in PCOS. FUNDING: INSERM (U1172), European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement n° 725149), CHU de Lille, France (Bonus H).
Assuntos
Síndrome do Ovário Policístico , Humanos , Animais , Camundongos , Feminino , Hormônio Luteinizante , Hormônio Antimülleriano , Imagem de Tensor de Difusão , Hormônio Liberador de Gonadotropina , Neuroglia/patologiaRESUMO
BACKGROUND: Dopamine responsiveness (dopa-sensitivity) is an important parameter in the management of patients with Parkinson's disease (PD). For quantification of this parameter, patients undergo a challenge test with acute Levodopa administration after drug withdrawal, which may lead to patient discomfort and use of significant resources. OBJECTIVE: Our objective was to develop a predictive model combining clinical scores and imaging. METHODS: 350 patients, recruited by 13 specialist French centers and considered for deep brain stimulation, underwent an acute L-dopa challenge (dopa-sensitivityâ>â30%), full assessment, and MRI investigations, including T1w and R2* images. Data were randomly divided into a learning base from 10 centers and data from the remaining centers for testing. A machine selection approach was applied to choose the optimal variables and these were then used in regression modeling. Complexity of the modelling was incremental, while the first model considered only clinical variables, the subsequent included imaging features. The performances were evaluated by comparing the estimated values and actual valuesResults:Whatever the model, the variables age, sex, disease duration, and motor scores were selected as contributors. The first model used them and the coefficients of determination (R2) was 0.60 for the testing set and 0.69 in the learning set (pâ<â0.001). The models that added imaging features enhanced the performances: with T1w (R2â=â0.65 and 0.76, pâ<â0.001) and with R2* (R2â=â0.60 and 0.72, pâ<â0.001). CONCLUSION: These results suggest that modeling is potentially a simple way to estimate dopa-sensitivity, but requires confirmation in a larger population, including patients with dopa-sensitivityâ<â30.
Assuntos
Levodopa , Doença de Parkinson , Antiparkinsonianos/uso terapêutico , Dopamina , Humanos , Levodopa/uso terapêutico , Imageamento por Ressonância Magnética , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/tratamento farmacológicoRESUMO
BACKGROUND: Parkinson's disease mild cognitive impairment (PD-MCI) is frequent and heterogenous. There is no consensus about its influence on subthalamic deep brain stimulation (STN-DBS) outcomes. OBJECTIVE: To determine the prevalence of PD-MCI and its subtypes in candidates to STN-DBS. Secondarily, we sought to identify MRI structural markers associated with cognitive impairment in these subgroups. METHODS: Baseline data from the French multicentric PREDISTIM cohort were used. Candidates to STN-DBS were classified according to their cognitive performance in normal cognition (PD-NC) or PD-MCI. The latter included frontostriatal (PD-FS) and posterior cortical (PD-PC) subtypes. Between-group comparisons were performed on demographical and clinical variables as well as on T1-weighted MRI sequences at the cortical and subcortical levels. RESULTS: 320 patients were included: 167 (52%) PD-NC and 153 (48%) PD-MCI patients. The latter group included 123 (80%) PD-FS and 30 (20%) PD-PC patients. There was no between-group difference regarding demographic and clinical variables. PD-PC patients had significantly lower global efficiency than PD-FS patients and significantly worse performance on visuospatial functions, episodic memory, and language. Compared to PD-NC, PD-MCI patients had cortical thinning and radiomic-based changes in the left caudate nucleus and hippocampus. There were no significant differences between the PD-MCI subtypes. CONCLUSION: Among the candidates to STN-DBS, a significant proportion has PD-MCI which is associated with cortical and subcortical alterations. Some PD-MCI patients have posterior cortical deficits, a subtype known to be at higher risk of dementia.
Assuntos
Disfunção Cognitiva , Estimulação Encefálica Profunda , Doença de Parkinson , Cognição , Disfunção Cognitiva/complicações , Disfunção Cognitiva/terapia , Humanos , Imageamento por Ressonância Magnética , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/terapiaRESUMO
Context: Cognitive impairments are common in patients with Parkinson's disease (PD) and are heterogeneous in their presentation. The "dual syndrome hypothesis" suggests the existence of two distinct subtypes of mild cognitive impairment (MCI) in PD: a frontostriatal subtype with predominant attentional and/or executive deficits and a posterior cortical subtype with predominant visuospatial, memory, and/or language deficits. The latter subtype has been associated with a higher risk of developing dementia. Objective: The objective of this study was to identify structural modifications in cortical and subcortical regions associated with each PD-MCI subtype. Methods: One-hundred and fourteen non-demented PD patients underwent a comprehensive neuropsychological assessment as well as a 3T magnetic resonance imaging scan. Patients were categorized as having no cognitive impairment (n = 41) or as having a frontostriatal (n = 16), posterior cortical (n = 25), or a mixed (n = 32) MCI subtype. Cortical regions were analyzed using a surface-based Cortical thickness (CTh) method. In addition, the volumes, shapes, and textures of the caudate nuclei, hippocampi, and thalami were studied. Tractometric analyses were performed on associative and commissural white matter (WM) tracts. Results: There were no between-group differences in volumetric measurements and cortical thickness. Shape analyses revealed more abundant and more extensive deformations fields in the caudate nuclei, hippocampi, and thalami in patients with posterior cortical deficits compared to patients with no cognitive impairment. Decreased fractional anisotropy (FA) and increased mean diffusivity (MD) were also observed in the superior longitudinal fascicle, the inferior fronto-occipital fascicle, the striato-parietal tract, and the anterior and posterior commissural tracts. Texture analyses showed a significant difference in the right hippocampus of patients with a mixed MCI subtype. Conclusion: PD-MCI patients with posterior cortical deficits have more abundant and more extensive structural alterations independently of age, disease duration, and severity, which may explain why they have an increased risk of dementia.
RESUMO
There is a growing need for surrogate biomarkers for Parkinson's disease (PD). Structural analysis using magnetic resonance imaging with T1-weighted sequences has the potential to quantify histopathological changes. Degeneration is typically measured by the volume and shape of morphological changes. However, these changes appear late in the disease, preventing their use as surrogate markers. We investigated texture changes in 108 individuals, divided into three groups, matched in terms of sex and age: (1) healthy controls (n = 32); (2) patients with early-stage PD (n = 39); and (3) patients with late-stage PD and severe L-dopa-related complications (n = 37). All patients were assessed in off-treatment conditions. Statistical analysis of first- and second-order texture features was conducted in the substantia nigra, striatum, thalamus and sub-thalamic nucleus. Regions of interest volumetry and voxel-based morphometry were performed for comparison. Significantly different texture features were observed between the three populations, with some showing a gradual linear progression between the groups. The volumetric changes in the two PD patient groups were not significantly different. Texture features were significantly associated with clinical scores for motor handicap. These results suggest that texture features, measured in the nigrostriatal pathway at PD diagnosis, may be useful in predicting clinical progression of motor handicap.