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1.
EMBO Mol Med ; 13(8): e13953, 2021 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-34254741

RESUMO

IgG4-related disease (IgG4-RD) is a fibroinflammatory disorder signified by aberrant infiltration of IgG4-restricted plasma cells into a variety of organs. Clinical presentation is heterogeneous, and pathophysiological mechanisms of IgG4-RD remain elusive. There are very few cases of IgG4-RD with isolated central nervous system manifestation. By leveraging single-cell sequencing of the cerebrospinal fluid (CSF) of a patient with an inflammatory intracranial pseudotumor, we provide novel insights into the immunopathophysiology of IgG4-RD. Our data illustrate an IgG4-RD-associated polyclonal T-cell response in the CSF and an oligoclonal T-cell response in the parenchymal lesions, the latter being the result of a multifaceted cell-cell interaction between immune cell subsets and pathogenic B cells. We demonstrate that CD8+ T effector memory cells might drive and sustain autoimmunity via macrophage migration inhibitory factor (MIF)-CD74 signaling to immature B cells and CC-chemokine ligand 5 (CCL5)-mediated recruitment of cytotoxic CD4+ T cells. These findings highlight the central role of T cells in sustaining IgG4-RD and open novel avenues for targeted therapies.


Assuntos
Doença Relacionada a Imunoglobulina G4 , Linfócitos B , Encéfalo , Linfócitos T CD8-Positivos , Humanos , Memória Imunológica
2.
Pathol Oncol Res ; 27: 643146, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34257609

RESUMO

Cells of the monocyte macrophage lineage form multinucleated giant cells (GCs) by fusion, which may express some cell cycle markers. By using a comprehensive marker set, here we looked for potential replication activities in GCs, and investigated whether these have diagnostic or clinical relevance in giant cell tumor of bone (GCTB). GC rich regions of 10 primary and 10 first recurrence GCTB cases were tested using immunohistochemistry in tissue microarrays. The nuclear positivity rate of the general proliferation marker, replication licensing, G1/S-phase, S/G2/M-phase, mitosis promoter, and cyclin dependent kinase (CDK) inhibitor reactions was analyzed in GCs. Concerning Ki67, moderate SP6 reaction was seen in many GC nuclei, while B56 and Mib1 positivity was rare, but the latter could be linked to more aggressive (p = 0.012) phenotype. Regular MCM6 reaction, as opposed to uncommon MCM2, suggested an initial DNA unwinding. Early replication course in GCs was also supported by widely detecting CDK4 and cyclin E, for the first time, and confirming cyclin D1 upregulation. However, post-G1-phase markers CDK2, cyclin A, geminin, topoisomerase-2a, aurora kinase A, and phospho-histone H3 were rare or missing. These were likely silenced by upregulated CDK inhibitors p15INK4b, p16INK4a, p27KIP1, p53 through its effector p21WAF1 and possibly cyclin G1, consistent with the prevention of DNA replication. In conclusion, the upregulation of known and several novel cell cycle progression markers detected here clearly verify early replication activities in GCs, which are controlled by cell cycle arresting CDK inhibitors at G1 phase, and support the functional maturation of GCs in GCTB.

3.
Sci Rep ; 11(1): 5529, 2021 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-33750857

RESUMO

Computer-assisted reporting (CAR) tools were suggested to improve radiology report quality by context-sensitively recommending key imaging biomarkers. However, studies evaluating machine learning (ML) algorithms on cross-lingual ontological (RadLex) mappings for developing embedded CAR algorithms are lacking. Therefore, we compared ML algorithms developed on human expert-annotated features against those developed on fully automated cross-lingual (German to English) RadLex mappings using 206 CT reports of suspected stroke. Target label was whether the Alberta Stroke Programme Early CT Score (ASPECTS) should have been provided (yes/no:154/52). We focused on probabilistic outputs of ML-algorithms including tree-based methods, elastic net, support vector machines (SVMs) and fastText (linear classifier), which were evaluated in the same 5 × fivefold nested cross-validation framework. This allowed for model stacking and classifier rankings. Performance was evaluated using calibration metrics (AUC, brier score, log loss) and -plots. Contextual ML-based assistance recommending ASPECTS was feasible. SVMs showed the highest accuracies both on human-extracted- (87%) and RadLex features (findings:82.5%; impressions:85.4%). FastText achieved the highest accuracy (89.3%) and AUC (92%) on impressions. Boosted trees fitted on findings had the best calibration profile. Our approach provides guidance for choosing ML classifiers for CAR tools in fully automated and language-agnostic fashion using bag-of-RadLex terms on limited expert-labelled training data.

4.
In Vivo ; 35(2): 1177-1183, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33622918

RESUMO

BACKGROUND: Crossed cerebellar diaschisis (CCD) is a phenomenon with depressed metabolism and hypoperfusion in the cerebellum. Using arterial spin-labelling perfusion weighted magnetic resonance imaging (ASL PWI), we investigated the frequency of CCD in patients with Alzheimer's disease (AD) and differences between patients with and without CCD. PATIENTS AND METHODS: In patients with AD who underwent a standardized magnetic resonance imaging including ASL PWI cerebral blood flow was evaluated in the cerebellum, and brain segmentation/volumetry was performed using mdbrain (mediaire GmbH, Berlin, Germany) and FSL FIRST (Functional Magnetic Resonance Imaging of the Brain Software Library). RESULTS: In total, 65 patients were included, and 22 (33.8%) patients were assessed as being CCD-positive. Patients with CCD had a significantly smaller whole brain volume (862.8±49.9 vs. 893.7±62.7 ml, p=0.049) as well as white matter volume (352.9±28.0 vs. 374.3±30.7, p=0.008) in comparison to patients without CCD. CONCLUSION: It was possible to detect CCD by ASL PWI in approximately one-third of patients with AD and was associated with smaller whole brain and white matter volume.


Assuntos
Doença de Alzheimer , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico por imagem , Cerebelo/diagnóstico por imagem , Circulação Cerebrovascular , Alemanha , Humanos , Imageamento por Ressonância Magnética , Perfusão , Marcadores de Spin
5.
In Vivo ; 35(1): 429-435, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33402493

RESUMO

BACKGROUND/AIM: Sodium (23Na) MR imaging is a noninvasive MRI technique that has been shown to be sensitive to visualize biochemical information about tissue viability, their cell integrity, and cell function in various studies. The aim of this study was to evaluate differences in regional brain 23Na signal intensity between Alzheimer's disease (AD) and healthy controls to preliminarily evaluate the capability of 23Na imaging as a biomarker for AD. PATIENTS AND METHODS: A total of 14 patients diagnosed with AD were included: 12 in the state of dementia and 2 with mild cognitive impairment (MCI), and 12 healthy controls (HC); they were all scanned on a 3T clinical scanner with a double tuned 1H/23Na birdcage head coil. After normalizing the signal intensity with that of the vitreous humor, relative tissue sodium concentration (rTSC) was measured after automated segmentation in the hippocampus, amygdala, basal ganglia, white matter (WM) and grey matter (GM) in both cerebral hemispheres. RESULTS: Patients with AD showed a significant increase in rTSC in comparison to healthy controls in the following brain regions: WM 13.6%; p=0.007, hippocampus 12.9%; p=0.003, amygdala 18.9%; p=0.0007. CONCLUSION: 23Na-MRI has the potential to be developed as a useful biomarker for the diagnosis of AD.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doença de Alzheimer/diagnóstico por imagem , Biomarcadores , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Sódio
6.
Clin Neuroradiol ; 31(3): 827-831, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32865598

RESUMO

PURPOSE: Occlusion or significant stenosis of the internal carotid artery (ICA) in the cervical segment is commonly associated with a poststenotic decrease in the downstream blood flow and perfusion. Fluid attenuated inversion recovery (FLAIR) vascular hyperintensities (FVH) are a phenomenon that represents slow arterial blood flow. In this study, we investigated the frequency and extent of FVH in the distal ICA in patients with proximal ICA stenosis. METHODS: We analyzed the magnetic resonance imaging (MRI) findings in 51 patients with a total of 60 cervical ICA stenoses with special focus on the frequency and extent of FVH in the area of the petrous segment of the ICA on FLAIR images and correlated these with Doppler/duplex sonography results. RESULTS: In 46 (76.7%) patients with ICA stenosis, FVH could be detected in the petrous segment of the ICA: in 19 (41.3%) patients a thin hyperintense rim near the vessel wall (grade 1), in 24 (52.2%) patients a strong hyperintense rim near the vessel wall (grade 2), and in 3 (6.5%) patients a hyperintense filling of the entire lumen (grade 3) was observed. The extent of FVH in the ICA in the petrous segment showed a high negative correlation with the poststenotic flow velocity (Spearman correlation, R = -0.75, p < 0.001), and moderate correlation with the degree of ICA stenosis (Spearman correlation, R = 0.51, p< 0.001). CONCLUSION: An FVH in the petrous ICA is commonly seen among patients with steno-occlusive disease in proximal ICA and could therefore be useful to recognize a proximal ICA stenosis even on FLAIR images.

7.
J Neuroimaging ; 31(2): 297-305, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33351997

RESUMO

BACKGROUND AND PURPOSE: To date, treatment response to stereotactic radiosurgery (SRS) in brain metastases (BM) can only be determined by MRI evaluation of contrast-enhancing lesions in a long-time follow-up. Sodium MRI has been a subject of immense interest in imaging research as the measure of tissue sodium concentration (TSC) can give valuable quantitative information on cell viability. We aimed to analyze the longitudinal changes of TSC in BM measured with 23 Na MRI before and after SRS for assessment of early local tumor effects. METHODS: Seven patients with a total of 12 previously untreated BM underwent SRS with 22 Gy. In addition to a standard MRI protocol including dynamic susceptibility-weighted contrast-enhanced perfusion, a 23 Na MRI was performed at three time points: (I) 2 days before, (II) 5 days, and (III) 40 days after SRS. Nine BMs were evaluated. The absolute TSC in the BM, the respective peritumoral edemas, and the normal-appearing corresponding contralateral brain area were assessed and the relative TSC were correlated to the changes in BM longest axial diameters. RESULTS: TSC was elevated in nine BM at baseline before SRS with a mean of 73.4 ± 12.3 mM. A further increase in TSC was observed 5 days after SRS in all the nine BM with a mean of 86.9 ± 13 mM. Eight of nine BM showed a mean 60.6 ± 13.3% decrease in the longest axial diameter 40 days after SRS; at this time point, the TSC also had decreased to a mean 65.1 ± 7.9 mM. In contrast, one of the nine BM had a 13.4% increase in the largest axial diameter at time point III. The TSC of this BM showed a further TSC increase of 80.1 mM 40 days after SRS. CONCLUSION: Changes in TSC using 23 Na MRI shows the possible capability to detect radiobiological changes in BM after SRS.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/metabolismo , Imageamento por Ressonância Magnética , Radiocirurgia , Sódio/metabolismo , Adulto , Idoso , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/radioterapia , Estudos de Viabilidade , Humanos , Masculino , Pessoa de Meia-Idade
9.
Oncology ; 98(1): 16-22, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31514200

RESUMO

PURPOSE: Preclinical studies indicated that imatinib may have single-agent activity in glioblastoma through inhibition of tyrosine kinase activity and also that it might enhance the efficacy of radiotherapy. We therefore sought to investigate clinical efficacy in patients with newly diagnosed and recurrent glioblastoma in combination with radiotherapy. METHODS: We conducted a nonrandomized, 2-arm, open-label phase II trial including patients aged 18 years or older with an ECOG performance status of 0-2 that were either newly diagnosed (arm A) with a measurable tumor (i.e., after incomplete resection or biopsy) or that were diagnosed with progression of a glioblastoma after initial therapy (arm B). Patients in arm A received 600 mg/day imatinib in combination with hypofractionated radiotherapy (2.5 Gy per fraction, 22 fractions). Patients in arm B received 600 mg/day imatinib alone or in combination with re-irradiation at various doses. In case tumor progression occurred, CCNU was added (2 cycles, 100 mg/m2) to imatinib. The primary end point was progression-free survival (PFS). The secondary end point was safety, defined as per Common Terminology Criteria for Adverse Events (version 2.0). Overall survival (OS) was analyzed as an exploratory end point. RESULTS: Fifty-one patients were enrolled, of which 19 were included in arm A and 32 in arm B. The median follow-up was 4 (0.5-30) months in arm A and 6.5 (0.3-51.5) months in arm B. The median PFS was 2.8 months (95% CI 0-8.7) in arm A and 2.1 months (95% CI 0-11.8) in arm B. The median OS was 5.0 (0.8-30) months (95% CI 0-24.1) in arm A and 6.5 (0.3-51.5) months (95% CI 0-32.5) in arm B. The major grade 3 events were seizure (present in 17 patients), pneumonia (11 patients), and vigilance decrease (7 patients). CONCLUSIONS: Imatinib showed no measurable activity in patients with newly diagnosed or recurrent glioblastoma.


Assuntos
Antineoplásicos/uso terapêutico , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Mesilato de Imatinib/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Biópsia , Terapia Combinada , Progressão da Doença , Feminino , Seguimentos , Glioblastoma/mortalidade , Glioblastoma/cirurgia , Humanos , Mesilato de Imatinib/administração & dosagem , Mesilato de Imatinib/efeitos adversos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Cuidados Pós-Operatórios , Prognóstico , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Retratamento , Resultado do Tratamento
10.
Anat Rec (Hoboken) ; 303(5): 1374-1392, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31336034

RESUMO

The Apidima 2 fossil cranium from South Peloponnese is one of the most important hominin specimens from Southeast Europe. Nevertheless, there has been continuous controversy as to whether it represents a so-called Preneandertal/Homo heidelbergensis such as, for example, the Petralona cranium from Northern Greece or a more derived Neandertal. Recent absolute dating evidence alone cannot clarify the issue because both classifications would be possible during the respective Middle Pleistocene time span. Since only limited data were available on the cranium, there have been repeated claims for the need of a broader comparative study of the hominin. The present article presents a CT-based virtual reconstruction including corrections of postmortem fractures and deformation as well as detailed metrical and morphological analyses of the specimen. Endocranial capacity could be estimated for the first time based on virtual reconstruction. Our multivariate analyses of metric data from the face and vault revealed close affinities to early and later Neandertals, especially showing the derived facial morphometrics. In addition, comparative analyses of Apidima 2 were done for many derived Neandertal features. Here again, a significant number of Neandertal features could be found in the Apidima cranium but no conditions common in Preneandertals. In agreement with a later Middle Pleistocene age Apidima is currently the earliest evidence of a hominin in Europe with such a derived Neandertal facial morphology. The place of Apidima in the complex process of Neandertal evolution as well as its taxonomic classification are discussed as well. Anat Rec, 303:1374-1392, 2020. © 2019 American Association for Anatomy.


Assuntos
Fósseis , Hominidae/anatomia & histologia , Crânio/anatomia & histologia , Animais , Evolução Biológica , Grécia , Processamento de Imagem Assistida por Computador , Homem de Neandertal/anatomia & histologia , Crânio/diagnóstico por imagem
11.
J Neuroradiol ; 47(2): 166-173, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30659892

RESUMO

BACKGROUND AND PURPOSE: Post-radiation treatment effects (pseudoprogression/radionecrosis) may bias MRI-based tumor response evaluation. To understand these changes specifically after high doses of radiotherapy, we analyzed MRIs of patients enrolled in the INTRAGO study (NCT02104882), a phase I/II dose-escalation trial of intraoperative radiotherapy (20-40 Gy) in glioblastoma. METHODS: INTRAGO patients were evaluated and compared to control patients who received standard therapy with focus on contrast enhancement patterns/volume, T2 lesion volume, and mean rCBV. RESULTS: Overall, 11/15 (73.3%) INTRAGO patients (median age 60 years) were included. Distant failure was observed in 7/11 (63.6%) patients, local tumor recurrence in one patient (9.1%). On the first follow-up MRI all but one patient demonstrated enhancement of varying patterns around the resection cavity which were: in 2/11 (18.2%) patients thin and linear, in 7/11 (63.6%) combined linear and nodular, and in 1/11 (9.1%) voluminous, indistinct, and mesh-like. In the course of treatment, most patients developed the latter two patterns (8/11 [72.7%]). INTRAGO patients demonstrated more often combined linear and nodular and/or voluminous, indistinct, mesh-like components (8/11 [72.7%]) in comparison to control patients (3/12 [25%], P = 0.02). INTRAGO patients demonstrated significantly increasing enhancing lesion (P = 0.001) and T2 lesion volumes (P < 0.001) in the longitudinal non-parametric analysis in comparison to the control group. rCBV showed no significant differences between both groups. CONCLUSIONS: High doses of radiotherapy to the tumor cavity result in more pronounced enhancement patterns/volumes and T2 lesion volumes. These results will be useful for the response evaluation of patients exposed to high doses of radiotherapy in future studies.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Glioblastoma/diagnóstico por imagem , Glioblastoma/radioterapia , Imageamento por Ressonância Magnética , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/radioterapia , Idoso , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Feminino , Glioblastoma/patologia , Glioblastoma/cirurgia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Resultado do Tratamento
12.
J Cereb Blood Flow Metab ; 40(11): 2265-2277, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-31752586

RESUMO

Longitudinal in vivo imaging studies characterizing subarachnoid hemorrhage (SAH)-induced large artery vasospasm (LAV) in mice are lacking. We developed a SAH-scoring system to assess SAH severity in mice using micro CT and longitudinally analysed LAV by intravenous digital subtraction angiography (i.v. DSA). Thirty female C57Bl/6J-mice (7 sham, 23 SAH) were implanted with central venous ports for repetitive contrast agent administration. SAH was induced by filament perforation. LAV was assessed up to 14 days after induction of SAH by i.v. DSA. SAH-score and neuroscore showed a highly significant positive correlation (rsp = 0.803, p < 0.001). SAH-score and survival showed a negative significant correlation (rsp = -0.71, p < 0.001). LAV peaked between days 3-5 and normalized on days 7-15. Most severe LAV was observed in the internal carotid (Δmax = 30.5%, p < 0.001), anterior cerebral (Δmax = 21.2%, p = 0.014), middle cerebral (Δmax = 28.16%, p < 0.001) and basilar artery (Δmax = 23.49%, p < 0.001). Cerebral perfusion on day 5 correlated negatively with survival time (rPe = -0.54, p = 0.04). Arterial diameter of the left MCA correlated negatively with cerebral perfusion on day 3 (rPe = -0.72, p = 0.005). In addition, pseudoaneurysms arising from the filament perforation site were visualized in three mice using i.v. DSA. Thus, micro-CT and DSA are valuable tools to assess SAH severity and to longitudinally monitor LAV in living mice.


Assuntos
Angiografia Cerebral , Artérias Cerebrais/diagnóstico por imagem , Artérias Cerebrais/fisiopatologia , Hemorragia Subaracnóidea/diagnóstico , Vasoespasmo Intracraniano/diagnóstico , Microtomografia por Raio-X , Animais , Biomarcadores , Biópsia , Angiografia Cerebral/métodos , Modelos Animais de Doenças , Feminino , Imuno-Histoquímica , Camundongos , Índice de Gravidade de Doença , Hemorragia Subaracnóidea/etiologia , Hemorragia Subaracnóidea/mortalidade , Microtomografia por Raio-X/métodos
13.
J Clin Neurosci ; 68: 268-270, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31204221

RESUMO

BACKGROUND: We investigated the frequency of blood-retina barrier impairment in optic neuritis (ON) using gadolinium leakage in ocular structures (GLOS), a novel imaging marker on contrast enhanced fluid attenuated inversion recovery images (FLAIR). METHODS: In 12 patients with acute ON who underwent repeated MRI the presence of GLOS was noted on contrast-enhanced FLAIR. RESULTS: Bilateral GLOS was observed in 4 (33.3%): in 3 symmetrical, and in 1 asymmetrical. In the latter GLOS was ipsilateral to the ON. CONCLUSIONS: GLOS may be observed frequently in ON. Asymmetrical GLOS may be caused by a more local effect of ON.


Assuntos
Gadolínio , Imageamento por Ressonância Magnética/métodos , Neurite Óptica/diagnóstico por imagem , Adulto , Idoso , Permeabilidade Capilar , Meios de Contraste , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neurite Óptica/patologia
15.
J Neurooncol ; 142(1): 103-109, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30565029

RESUMO

BACKGROUND AND PURPOSE: Gliomatosis cerebri (GC) is a rare growth pattern of glioblastoma whose diffuse nature is reflected by unspecific, relatively uniform findings on conventional MRI. In the present study we sought to evaluate the additional value of diffusion (DWI) and perfusion weighted (PWI) MRI for a more detailed characterization. METHODS: We analyzed the MRI findings in patients with histologically proven glioblastoma with GC growth pattern with a specific emphasis on T2 lesion pattern, volume, relative apparent diffusion coefficient (rACD), and relative cerebral blood volume (rCBV) and compared these to age-/gender-matched patients with localized glioblastoma. RESULTS: Overall, 16 patients (median age 59.5 years, 4 male) were included in the study. Of these, 8 patients had a glioblastoma with GC growth pattern, and 8 a classical localized growth pattern. While the median rADC (1.27 [IQR 1.12-1.41]) within the T2 lesion was significant lower in glioblastoma with GC growth pattern compared to localized glioblastoma (1.74 [IQR 1.45-1.96]; p = 0.003), the median T2 lesion volume and rCBV within the T2 lesion did not differ significantly. Furthermore, six patients with glioblastoma with GC growth pattern showed focal areas with significantly reduced rADC (p = 0.043), and/or increased rCBV (p = 0.028). CONCLUSIONS: Lower rADC in glioblastoma with GC growth pattern might reflect the diffuse tumor cell infiltration whereas focal areas with decreased rADC and/or increased rCBV probably indicate high tumor cell density and/or abnormal tumor vessels which may be useful for biopsy guidance.


Assuntos
Neoplasias Encefálicas/genética , Glioblastoma/diagnóstico por imagem , Neoplasias Neuroepiteliomatosas/diagnóstico por imagem , Idoso , Neoplasias Encefálicas/patologia , Feminino , Glioblastoma/patologia , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Neoplasias Neuroepiteliomatosas/patologia
16.
J Neuroradiol ; 46(1): 3-8, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30219336

RESUMO

PURPOSE: Aim of this study was to evaluate the collateral blood flow between more distal branches of the middle cerebral artery (MCA) in the case of peripheral MCA branch occlusion on dynamic 4D angiograms. We sought to individually predict the finally resulting infarction volume with regard to the extent of collateral blood flow. METHODS: Overall, 35 acute ischemic stroke patients with peripheral MCA branch occlusion were included. Volumes of the ischemic infarctions and perfusion deficits were measured on diffusion-weighted images DWI and time-to-peak TTP (> 4 s). Collateral flow on 4D MR angiograms were classified as previously specified. RESULTS: On DWI, the ischemic lesions had a mean volume of 3.4 ± 15.1 mL while the mean volume on TTP (> 4 s) was significantly larger 22.0 ± 18.1 mL (P < 0.001). On dynamic 4D angiograms we observed grade 1 in 8 (22.9%), grade 2 in 4 (11.4%), grade 3 in 10 (28.6%), and grade 4 in 13 (37.1%) patients. In comparison to patients with better collateralization (grade 3-4) patients with less sufficient collateralization (grade 0-2) demonstrated larger infarction volumes on initial (11.1 mL (IQR 2.9-35.5) vs. 2.1 mL (IQR 0.5-4.5), P = 0.03) and follow-up DWI (15.5 mL (IQR 12.6-23.3) vs. 1.9 mL (IQR 0.5-4.5), P = 0.03) with prominent infarction growth (7.4 mL (IQR 2.6-10.1) vs. 0.9 mL (IQR 0.2-2.6), P = 0.08). CONCLUSIONS: In the majority of cases with distal MCA branch occlusion a good collateral blood flow has been observed. Nevertheless, in approximately one quarter of patients an insufficient collateral blood flow has been detected that was associated with substantial infarction growth.


Assuntos
Circulação Colateral , Imagem de Difusão por Ressonância Magnética/métodos , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Angiografia por Ressonância Magnética/métodos , Acidente Vascular Cerebral/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Angiografia Cerebral , Meios de Contraste , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Imageamento Tridimensional , Masculino , Meglumina , Pessoa de Meia-Idade , Compostos Organometálicos , Estudos Prospectivos
17.
Neurosurgery ; 84(1): 41-49, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29528443

RESUMO

BACKGROUND: The median time to recurrence of glioblastoma (GB) following multimodal treatment is ∼7 mo. Nearly all cancers recur locally, suggesting that augmenting local treatments may improve outcomes. OBJECTIVE: To investigate whether intraoperative radiotherapy (IORT) to the resection cavity is safe and effective. METHODS: INTRAGO was a phase I/II trial to evaluate the safety and tolerability of IORT with 20 to 40 Gy of low-energy photons in addition to standard radiochemotherapy (ClinicalTrials.gov ID, NCT02685605). The primary endpoint was safety as per occurrence of dose-limiting toxicities. Secondary endpoints were progression-free survival (PFS) and overall survival (OS). We also performed an exploratory analysis of the local PFS (L-PFS), defined as recurrence within 1 cm of the treated margin. RESULTS: Fifteen patients were treated at 3 dose levels. Of these, 13 underwent incomplete resection, 6 had unresected satellites, and 3 did not receive per-protocol treatment (PPT). The MGMT promoter was unmethylated in 10 patients. The median follow-up was 13.8 mo. The majority of grade 3 to 5 adverse events were deemed unrelated to IORT. Five cases of radionecrosis were observed, 2 were classified as grade 3 events. Other grade 3 events judged related to radiotherapy (external-beam radiotherapy and/or IORT) were wound dehiscence (n = 1), CSF leakage (n = 1), cyst formation (n = 1). No IORT-related deaths occurred. The median PFS was 11.2 mo (95% confidence interval [CI]: 5.4-17.0) for all patients and 11.3 mo (95% CI: 10.9-11.6) for those receiving PPT. The median L-PFS was 14.3 mo (95% CI: 8.4-20.2) for all patients and 17.8 mo (95% CI: 9.7-25.9) for those receiving PPT. The median OS was 16.2 mo (95% CI: 11.1-21.4) for all patients and 17.8 mo (95% CI: 13.9-21.7) for those receiving PPT. CONCLUSION: These data suggest that IORT is associated with manageable toxicity. Considering the limitations of a 15-patient phase I/II trial, further studies aimed at assessing an outcome benefit are warranted.


Assuntos
Neoplasias Encefálicas/radioterapia , Glioblastoma/radioterapia , Cuidados Intraoperatórios , Radioterapia/métodos , Idoso , Quimiorradioterapia , Terapia Combinada , Relação Dose-Resposta à Radiação , Determinação de Ponto Final , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Radioterapia/efeitos adversos , Resultado do Tratamento
18.
Mult Scler ; 25(6): 792-800, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-29683029

RESUMO

BACKGROUND: Leptomeningeal contrast enhancement on fluid-attenuated inversion recovery (FLAIR) images has been reported in patients with multiple sclerosis and interpreted as a biomarker of inflammation. In this study, we sought to evaluate this phenomenon in patients with optic neuritis (ON). METHODS: A total of 42 patients with suspected ON were included in this prospective study and underwent a dedicated study magnetic resonance imaging (MRI) protocol including native and contrast-enhanced fat-suppressed thin-section axial and coronal FLAIR images on an 1.5 T magnetic resonance (MR) system. RESULTS: After diagnostic workup, 34 patients with final diagnosis of ON were analyzed in detail. On contrast-enhanced fat-suppressed FLAIR images, 25 (73.5%) patients with ON demonstrated perioptic leptomeningeal enhancement, and in 3 (8.8%) patients, this was even the only pathological MRI finding. In comparison, patients with perioptic leptomeningeal enhancement on contrast-enhanced fat-suppressed FLAIR images had a higher prevalence of additional hyperintense brain lesions ( p = 0.022) as well as cerebrospinal fluid (CSF)-specific oligoclonal bands ( p = 0.013) than patients without. CONCLUSION: Perioptic leptomeningeal contrast enhancement on fat-suppressed FLAIR images is a novel marker in ON and possibly reflects a leptomeningeal inflammatory process preceding or accompanying ON. Thin-section contrast-enhanced fat-suppressed FLAIR images might be a useful addition in MRI protocols for patients with suspected ON.


Assuntos
Imageamento por Ressonância Magnética , Meninges/diagnóstico por imagem , Neurite Óptica/diagnóstico por imagem , Adulto , Biomarcadores , Feminino , Humanos , Aumento da Imagem , Masculino , Pessoa de Meia-Idade , Adulto Jovem
19.
Neurosurgery ; 84(5): 1133-1137, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29688510

RESUMO

BACKGROUND: Glioblastoma (GBM) is the most common malignant brain tumor in adult patients. Tumor recurrence commonly occurs around the resection cavity, especially after subtotal resection (STR). Consequently, the extent of resection correlates with overall survival (OS), suggesting that depletion of postoperative tumor remnants will improve outcome. OBJECTIVE: To assess safety and efficacy of adding stereotactic radiosurgery (SRS) to the standard treatment of GBM in patients with postoperative residual tumor. METHODS: Gamma-GBM is a single center, open-label, prospective, single arm, phase II study that includes patients with newly diagnosed GBM (intraoperative via frozen sections) who underwent STR (residual tumor will be identified by native and contrast enhanced T1-weighted magnetic resonance imaging scans). All patients will receive SRS with 15 Gy (prescribed to the 50% isodose enclosing all areas of residual tumor) early (within 24-72 h) after surgery. Thereafter, all patients undergo standard-of-care therapy for GBM (radiochemotherapy with 60 Gy external beam radiotherapy [EBRT] plus concomitant temozolomide and 6 cycles of adjuvant temozolomide chemotherapy). The primary outcome is median progression-free survival, secondary outcomes are median OS, occurrence of radiation induced acute (<3 wk), early delayed (<3 mo), and late (>3 mo post-SRS) neurotoxicity and incidence of symptomatic radionecrosis. EXPECTED OUTCOMES: We expect to detect efficacy and safety signals by the immediate application of SRS to standard-of-care therapy in newly diagnosed GBM. DISCUSSION: Early postoperative SRS to areas of residual tumor could bridge the therapeutic gap between surgery and adjuvant therapies.


Assuntos
Neoplasias Encefálicas/cirurgia , Glioblastoma/cirurgia , Neoplasia Residual/cirurgia , Radiocirurgia/métodos , Adulto , Idoso , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Quimiorradioterapia Adjuvante/métodos , Feminino , Glioblastoma/mortalidade , Glioblastoma/patologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasia Residual/mortalidade , Intervalo Livre de Progressão , Estudos Prospectivos , Lesões por Radiação/epidemiologia , Lesões por Radiação/etiologia , Radiocirurgia/efeitos adversos , Radiocirurgia/mortalidade , Projetos de Pesquisa
20.
Stroke ; : STROKEAHA118023573, 2018 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-30580698

RESUMO

Background and Purpose- We investigated the frequency and pattern of blood-brain barrier, as well as blood-retina barrier, impairment in acute lacunar infarction as demonstrated by hyperintense acute reperfusion marker and gadolinium leakage in ocular structures (GLOS), respectively, on fluid-attenuated inversion recovery images. Methods- Acute lacunar infarction patients who underwent repeated magnetic resonance imaging after intravenous contrast agent administration were identified and the presence of GLOS in the anterior chamber and vitreous body and hyperintense acute reperfusion marker noted on fluid-attenuated inversion recovery. Results- Overall, 24 acute lacunar infarction patients (median age 64.5 years; interquartile range, 54-78 years) were included. On contrast-enhanced fluid-attenuated inversion recovery, GLOS was observed in 11 (45.8%) patients: in 4 (16.7%) in the anterior chamber only and in 7 (29.2%) in the anterior chamber and vitreous body. In all patients, GLOS was bilateral and symmetrical. In patients with GLOS in the anterior chamber only, the time between initial and follow-up magnetic resonance imaging was significantly shorter (7.5 [interquartile range, 4.25-11.5] hours) compared with patients with GLOS in the anterior chamber and vitreous body (28 [interquartile range, 10-43] hours; P=0.047). Hyperintense acute reperfusion marker could not be demonstrated in any of the patients. Conclusions- In acute lacunar infarction patients, unlike hyperintense acute reperfusion marker, GLOS is a frequent finding and shows a similar temporal evolution like in larger ischemic stroke.

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