Revistas
Revista:
NMR IN BIOMEDICINE
ISSN:
0952-3480
Resection control in brain tumor surgery can be achieved in real time with intraoperative MRI (iMRI). Arterial spin labeling (ASL), a technique that measures cerebral blood flow (CBF) non-invasively without the use of intravenous contrast agents, can be performed intraoperatively, providing morpho-physiological information. This study aimed to evaluate the feasibility, image quality and potential to depict residual tumor of a pseudo-continuous ASL (PCASL) sequence at 3 T. Seventeen patients with brain tumors, primary (16) or metastatic (1), undergoing resection surgery with iMRI monitoring, were prospectively recruited (nine men, age 56 ± 16.6 years). A PCASL sequence with long labeling duration (3000 ms) and postlabeling delay (2000 ms) was added to the conventional protocol, which consisted of pre- and postcontrast 3D T1 -weighted (T1w) images, optional 3D-FLAIR, and diffusion. Three observers independently assessed the image quality (four-point scale) of PCASL-derived CBF maps. In those with diagnostic quality (Scores 2-4) they evaluated the presence of residual tumor using the conventional sequences first, and the CBF maps afterwards (three-point scale). Inter-observer agreement for image quality and the presence of residual tumor was assessed using Fleiss kappa statistics. The intraoperative CBF ratio of the surgical margins (i.e., perilesional CBF values normalized to contralateral gray matter CBF) was compared with preoperative CBF ratio within the tumor (Wilcoxon's test). Diagnostic ASL image quality was observed in 94.1% of patients (interobserver Fleiss ¿ = 0.76). PCASL showed additional foci suggestive of high-grade residual component in three patients, and a hyperperfused area extending outside the enhancing component in one patient. Interobserver agreement was almost perfect in the evaluation of residual tumor with the conventional sequences (Fleiss ¿ = 0.92) and substantial for PCASL (Fleiss ¿ = 0.80). No significant differences were found between pre and intraoperative CBF ratios (p = 0.578) in patients with residual tumor (n = 7). iMRI-PCASL perfusion is feasible at 3 T and is useful for the intraoperative assessment of residual tumor, providing in some cases additional information to the conventional sequences.
Revista:
JOURNAL OF ALZHEIMERS DISEASE
ISSN:
1387-2877
Año:
2023
Vol.:
93
N°:
1
Págs.:
125 - 140
Background: Subjective cognitive decline (SCD) may represent a preclinical stage of Alzheimer's disease (AD). Predicting progression of SCD patients is of great importance in AD-related research but remains a challenge. Objective: To develop and implement an ensemble machine learning (ML) algorithm to identify SCD subjects at risk of conversion to mild cognitive impairment (MCI) or AD. Methods: Ninety-nine SCD patients were included. Thirty-two progressed to MCI/AD, while 67 remained stable. To minimize the effect of class imbalance, both classes were balanced, and sensitivity was taken as evaluation metric. Bagging and boosting ML models were developed by using socio-demographic and clinical information, Mini-Mental State Examination and Geriatric Depression Scale (GDS) scores (feature-set 1a); socio-demographic characteristics and neuropsychological tests scores (feature-set 1b) and regional magnetic resonance imaging grey matter volumes (feature-set 2). The most relevant variables were combined to find the best model. Results: Good prediction performances were obtained with feature-sets 1a and 2. The most relevant variables (variable importance exceeding 20%) were: Age, GDS, and grey matter volumes measured in four cortical regions of interests. Their combination provided the optimal classification performance (highest sensitivity and specificity) ensemble ML model, Extreme Gradient Boosting with over-sampling of the minority class, with performance metrics: sensitivity = 1.00, specificity = 0.92 and area-under-the-curve = 0.96. The median values based on fifty random train/test splits were sensitivity = 0.83 (interquartile range (IQR) = 0.17), specificity = 0.77 (IQR = 0.23) and area-under-the-curve = 0.75 (IQR = 0.11). Conclusion: A high-performance algorithm that could be translatable into practice was able to predict SCD conversion to MCI/AD by using only six predictive variables.
Revista:
EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY
ISSN:
0937-4477
Año:
2022
Vol.:
279
N°:
12
Págs.:
5591 - 5600
Purpose: Current studies show that frequency tuning modification is a good marker for the detection of endolymphatic hydrops (EH) employing magnetic resonance imaging (MRI) in patients with Ménière's disease (MD). The purpose of the present study is to analyze the auditory and vestibular function with audiometric and vestibular-evoked myogenic potentials (VEMP) responses, respectively, in both the affected and unaffected ears of patients with unilateral MD using MRI as diagnostic support for the degree of EH.
Methods: We retrospectively reviewed the medical records of 76 consecutive patients with unilateral definite MD (age 55 (28-75); 39 women, 37 men). MRI was used through intravenous gadolinium administration, audiometry, and VEMPs. Functional tests were performed up to a week after the MRI. All were followed up one year after imaging utilizing clinical, auditory, and vestibular testing to rule out bilateral involvement.
Results: In the unaffected ear, the mean pure-tone average is normal even in cases with hydrops and, for a similar severity of hydrops is significantly lower than in the affected ear. Significant differences for the amplitude of the response at 0.5 kHz, at 1 kHz between the affected and unaffected ears were found to be lower in the affected ears. The relative amplitude ratio (1 Kz-0.5 kHz) was significantly lower in the affected ear and in the case of the oVEMP response depends on the degree of EH. The response in the unaffected ear was not modified by the presence or the degree of hydrops.
Conclusion: In the unaffected ear, hydrops is not associated with hearing deterioration. For a similar degree of hydrops, hearing loss is significantly greater in the affected ear. The endolymphatic hydrops in the vestibule induces a frequency bias in the VEMP response only in the affected ear and not in the unaffected ear. Because of these findings we consider that hydrops does not represent an active disorder in the unaffected ear.
Revista:
FRONTIERS IN PHYSIOLOGY
ISSN:
1664-042X
Año:
2021
Vol.:
12
Págs.:
621720
A pseudocontinuous arterial spin labeling (PCASL) sequence combined with background suppression and single-shot accelerated 3D RARE stack-of-spirals was used to evaluate cerebrovascular reactivity (CVR) induced by breath-holding (BH) in ten healthy volunteers. Four different models designed using the measured change in PETCO2 induced by BH were compared, for CVR quantification. The objective of this comparison was to understand which regressor offered a better physiological model to characterize the cerebral blood flow response under BH. The BH task started with free breathing of 42 s, followed by interleaved end-expiration BHs of 21 s, for ten cycles. The total scan time was 12 min and 20 s. The accelerated readout allowed the acquisition of PCASL data with better temporal resolution than previously used, without compromising the post-labeling delay. Elevated CBF was observed in most cerebral regions under hypercapnia, which was delayed with respect to the BH challenge. Significant statistical differences in CVR were obtained between the different models in GM (p < 0.0001), with ramp models yielding higher values than boxcar models and between the two tissues, GM and WM, with higher values in GM, in all the models (p < 0.0001). The adjustment of the ramp amplitude during each BH cycle did not improve the results compared with a ramp model with a constant amplitude equal to the mean PETCO2 change during the experiment.
Revista:
FRONTIERS IN SURGERY
ISSN:
2296-875X
Año:
2021
Vol.:
8
Págs.:
673847
Background: Endolymphatic hydrops (EH) is the histopathological hallmark of Ménière's disease (MD) and has been found by in vivo magnetic resonance imaging (MRI) in patients with several inner ear syndromes without definite MD criteria. The incidence and relevance of this finding is under debate. Purpose: The purpose of the study is to evaluate the prevalence and characteristics of EH and audiovestibular test results in groups of patients with fluctuating audiovestibular symptoms not fulfilling the actual criteria for definite MD and compare them with a similar group of patients with definite MD and a group of patients with recent idiopathic sudden neurosensory hearing loss (ISSNHL). Material and Methods: 170 patients were included, 83 with definite MD, 38 with fluctuating sensorineural hearing loss, 34 with recurrent vertigo, and 15 with ISSNHL. The clinical variables, audiovestibular tests, and EH were evaluated and compared. Logistic proportional hazard models were used to obtain the odds ratio for hydrops development, including a multivariable adjusted model for potential confounders. Results: No statistical differences between groups were found regarding disease duration, episodes, Tumarkin spells, migraine, vascular risk factors, or vestibular tests; only hearing loss showed differences. Regarding EH, we found significant differences between groups, with odds ratio (OR) for EH presence in definite MD group vs. all other patients of 11.43 (4.5-29.02; p < 0.001). If the ISSNHL group was used as reference, OR was 55.2 (11.9-253.9; p < 0.001) for the definite MD group, 9.9 (2.1-38.9; p = 0.003) for the recurrent vertigo group, and 5.1 (1.2-21.7; p = 0.03) for the group with fluctuating sensorineural hearing loss. Conclusion: The percentage of patients with EH varies between groups. It is minimal in the ISSNHL group and increases in groups with increasing fluctuating audiovestibular symptoms, with a rate of severe EH similar to the known rate of progression to definite MD in those groups, suggesting that presence of EH by MRI could be related to the risk of progression to definite MD. Thus, EH imaging in these patients is recommended.
Revista:
ANNALS OF BIOMEDICAL ENGINEERING
ISSN:
0090-6964
Año:
2021
Vol.:
49
N°:
2
Págs.:
746 - 756
Imaging of small laboratory animals in clinical MRI scanners is feasible but challenging. Compared with dedicated preclinical systems, clinical scanners have relatively low B(0)field (1.5-3.0 T) and gradient strength (40-60 mT/m). This work explored the use of wireless inductively coupled coils (ICCs) combined with appropriate pulse sequence parameters to overcome these two drawbacks, with a special emphasis on the optimization of the coil passive detuning circuit for this application. A Bengal rose photothrombotic stroke model was used to induce cortical infarction in rats and mice. Animals were imaged in a 3T scanner using T2 and T1-weighted sequences. In all animals, the ICCs allowed acquisition of high-quality images of the infarcted brain at acute and chronic stages. Images obtained with the ICCs showed a substantial increase in SNR compared to clinical coils (by factors of 6 in the rat brain and 16-17 in the mouse brain), and the absence of wires made the animal preparation workflow straightforward.
Revista:
ACTA OTO-LARYNGOLOGICA
ISSN:
0001-6489
Año:
2020
Vol.:
140
N°:
11
Págs.:
883-888
Background The main sequences used to assess degree of endolymphatic hydrops (EH) are the 3D- inversion-recovery (IR) with real reconstruction and the 3D- fluid-attenuated inversion recovery (FLAIR). Objectives The purpose of this study is to describe and compare both sequences. Material and methods Forty-two consecutive patients diagnosed with probable or definite Menier ' s disease were referred for hydrops MR examination. Vestibular and cochlear EH in both sequences were read by two independent radiologists, unaware of the patient's clinical status. The primary study endpoint was the concordance in the hydrops detection and severity with both imaging sequences. This was assessed using the Cohen's kappa Kappa statistic for disease grading and Pearson X(2)test to test the difference in detection rates of hydrops. Statistical significance was defined as two-sidedp < .05. Results We obtained an excellent overall concordance, with a kappa of 0.821, (p < .001) when comparing hydrops detection. The degree of concordance is higher in vestibular hydrops than in cochlear hydrops. The 3D-IR sequence detected more hydrops than the 3D FLAIR, (62 vs. 39.5%,p < .03). Conclusion The 3D-IR sequence seems to be superior to the 3D-FLAIR for the assessment of EH. Significance:The 3D-IR sequence should be considered as a standalone parameter for a shorter and optimized EH magnetic resonance imaging protocol.
Revista:
BMC CARDIOVASCULAR DISORDERS
ISSN:
1471-2261
Año:
2020
Vol.:
20
N°:
1
Págs.:
93
Background Major adverse cardiovascular events are the main cause of morbidity and mortality over the long term in patients undergoing carotid endarterectomy. There are few reports assessing the prognostic value of markers of inflammation in relation to the risk of cardiovascular disease after carotid endarterectomy. Here, we aimed to determine whether matrix metalloproteinases (MMP-1, MMP-2, MMP-7, MMP-9 and MMP-10), tissue inhibitor of MMPs (TIMP-1) and in vivo inflammation studied by F-18-FDG-PET/CT predict recurrent cardiovascular events in patients with carotid stenosis who underwent endarterectomy. Methods This prospective cohort study was carried out on 31 consecutive patients with symptomatic (23/31) or asymptomatic (8/31) severe (> 70%) carotid stenosis who were scheduled for carotid endarterectomy between July 2013 and March 2016. In addition, 26 healthy controls were included in the study. Plasma and serum samples were collected 2 days prior to surgery and tested for MMP-1, MMP-2, MMP-7, MMP-9, MMP-10, TIMP-1, high-density lipoprotein, low-density lipoprotein, high-sensitivity C-reactive protein and erythrocyte sedimentation rate. F-18-FDG-PET/CT focusing on several territories' vascular wall metabolism was performed on 29 of the patients because of no presurgical availability in 2 symptomatic patients. Histological and immunohistochemical studies were performed with antibodies targeting MMP-10, MMP-9, TIMP-1 and CD68. Results The patients with carotid stenosis had significantly more circulating MMP-1, MMP-7 and MMP-10 than the healthy controls. Intraplaque TIMP-1 was correlated with its plasma level (r = 0.42 P = .02) and with F-18-FDG uptake (r = 0.38 P = .05). We did not find any correlation between circulating MMPs and in vivo carotid plaque metabolism assessed by F-18-FDG-PET. After a median follow-up of 1077 days, 4 cerebrovascular, 7 cardiovascular and 11 peripheral vascular events requiring hospitalization were registered. Circulating MMP-7 was capable of predicting events over and above the traditional risk factors (HR = 1.15 P = .006). When the model was associated with the variables of interest, the risk predicted by F-18-FDG-PET was not significant. Conclusions Circulating MMP-7 may represent a novel marker for recurrent cardiovascular events in patients with moderate to severe carotid stenosis. MMP-7 may reflect the atherosclerotic burden but not plaque inflammation in this specific vascular territory.
Revista:
AURIS NASUS LARYNX
ISSN:
0385-8146
Año:
2019
Vol.:
46
N°:
2
Págs.:
210 - 217
Objectives
It has been suggested that in Ménière¿s disease (MD) a dissociated result in the caloric test (abnormal result) and video head-impulse test (normal result) probably indicates that hydrops affects the membranous labyrinth in the horizontal semicircular canal (HSC). The hypothesis in this study is that based on endolymphatic hydrops¿ cochleocentric progression, hydrops should also be more severe in the vestibule of these patients than in those for whom both tests are normal.
Methods
22 consecutive patients with unilateral definite MD were included and classified as NN if both tests were normal or AN if the caloric test was abnormal. MRI evaluation of endolymphatic hydrops was carried out with a T2-FLAIR sequence performed 4 h after intravenous gadolinium administration. The laterality and degree of vestibular endolymphatic hydrops and the presence or absence of cochlear endolymphatic hydrops were recorded. Demographic data, audiometric and vestibular evoked myogenic potentials were collected, and video head-impulse and caloric tests were performed.
Results
Patients in both groups (NN and AN) were similar in terms of demographic data and hearing loss. The interaural asymmetry ratio was significantly higher for ocular and cervical VEMP in patients in the AN group. There was a significantly higher degree of hydrops in the vestibule of the affected ear of AN patients (¿2; p = 0.028).
Conclusion
Significant canal paresis in the caloric test is associated with more sev
Revista:
PLOS ONE
ISSN:
1932-6203
Año:
2019
Vol.:
14
N°:
6
Págs.:
e0217881
Background Hypofractionated radiation therapy is a feasible and safe treatment option in elderly and frail patients with glioblastoma. The aim of this study was to evaluate the effectiveness of hypofractionated radiation therapy with concurrent temozolomide in terms of feasibility and disease control in primary glioblastoma patients with poor prognostic factors other than advanced age, such as post-surgical neurological complications, high tumor burden, unresectable or multifocal lesions, and potential low treatment compliance due to social factors or rapidly progressive disease. Material and methods GTV included the surgical cavity plus disease visible in T1WI-MRI, FLAIR-MRI and in the MET-uptake. The CTV was defined as the GTV plus 1.5-2 cm margin; the PTV was the CTV+0.3 cm margin. Forty, fourty-five, and fifty grays in 15 fractions were prescribed to 95% of PTV, CTV, and GTV, respectively. Treatment was delivered using IMRT or the VMAT technique. Simultaneously, 75 mg/m(2)/day of temozolomide were administered. Results Between January 2010 and November 2017, we treated a total of 17 patients. The median age at diagnosis was 68-years; median KPS was 50-70%. MGMT-methylation status was negative in 5 patients, and 8 patients were IDH-wildtype. Eight of 18 patients were younger than 65-years. Median tumor volume was 26.95cc; median PTV volume was 322cc. Four lesions were unresectable; 6 patients underwent complete surgical resection. Median residual volume was 1.14cc. Progression-free survival was 60% at 6 months, 33% at 1-year and 13% at 2-years (median OS = 7 months). No acute grade 3-5 toxicities were documented. Symptomatic grade 3 radiation necrosis was observed in one patient. Conclusions Patients with poor clinical factors other than advanced age can be selected for hypofractionated radiotherapy. The OS and PFS rates obtained in our series are similar to those in patients treated with standard fractionation, assuring good treatment adherence, low rates of toxicity and probable improved cost-effectiveness.
Revista:
MEDICINE (ELSEVIER)
ISSN:
0304-5412
Año:
2019
Vol.:
12
N°:
70
Págs.:
4108 - 4119
El ictus isquémico de causa inhabitual representa el 8% de los infartos y el 30% en los adultos jóvenes. Se caracteriza por su heterogeneidad etiológica y puede ser la primera manifestación de la enfermedad de base o una complicación evolutiva más. Los síntomas/signos asociados a la enfermedad subyacente suelen orientar el diagnóstico. El tratamiento es el de la enfermedad de base, si resulta posible, y los fármacos antitrombóticos. La oclusión trombótica de las venas encefálicas y senos durales es más frecuente en adultos jóvenes y predomina en las mujeres (3:1). Las trombofilias hereditarias, embarazo y puerperio, anticonceptivos orales, neoplasias, arteriopatías inflamatorias e infecciones son los principales factores de riesgo. El síntoma más frecuente es la cefalea. Los principales síndromes de presentación son: hipertensión intracraneal aislada, encefalopatía subaguda y cuadro focal. Se trata con anticoagulantes y su pronóstico es generalmente bueno.
Revista:
REVISTA DE NEUROLOGIA
ISSN:
0210-0010
Año:
2018
Vol.:
66
N°:
Supl. 1
Págs.:
S83 - S89
AIM:
To contribute to neuropsychological profiling of developmental amnesia subsequent to bilateral damage to both hippocampi in early age.
SUBJECTS AND METHODS:
The total sample of 24 schoolchildren from both sexes is distributed in three groups: perinatal hypoxic-ischaemic encephalopathy and everyday complaints of memory in school age (n = 8); perinatal hypoxic-ischaemic encephalopathy without memory complaints (n = 7); and a group of typically developing (n = 9). All participants in every groups did have normal general intelligence and attention. Both clinical groups had, as another clinical consequence, spastic cerebral palsy (diplegia). Neuropsychological exam consisted on tests of general intelligence, attentional abilities, declarative memory and semantic knowledge. All participants had a brain magnetic resonance image and spectroscopy of hippocampi. Scheltens criteria were used for visual estimation of hippocampal atrophy. Parametric and non-parametric statistical contrasts were made.
RESULTS:
Despite preservation of semantic and procedural learning, declarative-episodic memory is impaired in the first group versus the other two groups. A significant proportion of bilateral hippocampal atrophy is only present in the first group versus the other two non-amnesic groups using Scheltens estimation on MRI. Two cases without evident atrophy did have diminished NAA/(Cho + Cr) index in both hippocampi.
CONCLUSIONS:
Taken together, these results contribute to delineate developmental amnesia as an specific impairment due to early partial bihippocampal damage, in agreement with previous studies. After diagnosis of developmental amnesia, a specific psychoeducational intervention must be made; also this impairment could be candidate for pharmacological trials in the future.
Revista:
JOURNAL OF INTERNATIONAL ADVANCED OTOLOGY
ISSN:
1308-7649
Año:
2018
Vol.:
14
N°:
2
Págs.:
334 - 336
Different types of otic capsule dehiscence restricted to the cochlea have been described. Here we describe the case of a patient with a cochlear-internal auditory canal dehiscence associated with a cochlear-facial dehiscence not reported before. A 53-year-old patient with severe to profound sensor ineural hearing loss due to bilateral Meniere's disease under went a cochlear implant surgery on the right ear. Preoperative brain magnetic resonance imaging findings were reported to be normal; dur ing surgery, a cerebrospinal fluid gusher occur red at the time of round window opening. Postoperative computed tomography imaging showed a bony dehiscence at two levels of the otic capsule.
Revista:
FRONTIERS IN ONCOLOGY
ISSN:
2234-943X
Año:
2018
Vol.:
12
N°:
8
Págs.:
61
Diffuse intrinsic pontine gliomas (DIPGs) are aggressive glial brain tumors that primarily affect children, for which there is no curative treatment. Median overall survival is only one year. Currently, the scientific focus is on expanding the knowledge base of the molecular biology of DIPG, and identifying effective therapies. Oncolytic adenovirus DNX-2401 is a replication-competent, genetically modified virus capable of infecting and killing glioma cells, and stimulating an anti-tumor immune response. Clinical trials evaluating intratumoral DNX-2401 in adults with recurrent glioblastoma have demonstrated that the virus has a favorable safety profile and can prolong survival. Subsequently, these results have encouraged the transition of this biologically active therapy from adults into the pediatric population. To this aim, we have designed a clinical Phase I trial for newly diagnosed pediatric DIPG to investigate the feasibility, safety, and preliminary efficacy of delivering DNX-2401 into tumors within the pons following biopsy. This case report presents a pediatric patient enrolled in this ongoing Phase I trial for children and adolescents with newly diagnosed DIPG. The case involves an 8-year-old female patient with radiologically diagnosed DIPG who underwent stereotactic tumor biopsy immediately followed by intratumoral DNX-2401 in the same biopsy track. Because there were no safety concerns or new neurological deficits, the patient was discharged 3¿days after the procedures. To our knowledge, this is the first report of intratumoral DNX-2401 for a patient with DIPG in a clinical trial. We plan to demonstrate that intratumoral delivery of an oncolytic virus following tumor biopsy for pediatric patients with DIPG is a novel and feasible approach and that DNX-2401 represents an innovative treatment for the disease.
Revista:
EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY
ISSN:
0937-4477
Año:
2018
Vol.:
275
N°:
1
Págs.:
311 - 312
Revista:
RADIOLOGIA
ISSN:
0033-8338
Año:
2018
Vol.:
60
N°:
2
Págs.:
136 - 142
Objective: To report our experience in the use of 3 testa intraoperative magnetic resonance imaging (MRI) in neurosurgical procedures for tumors, and to evaluate the criteria for increasing the extension of resection. Material and methods: This retrospective study included all consecutive intraoperative MRI studies done for neuro-oncologic disease in the first 13 months after the implementation of the technique. We registered possible immediate complications, the presence of tumor remnants, and whether the results of the intraoperative MRI study changed the surgical management. We recorded the duration of surgery in all cases. Results: The most common tumor was recurrent glioblastoma, followed by primary glioblastoma and metastases. Complete resection was achieved in 28%, and tumor remnants remained in 72%. Intraoperative MRI enabled neurosurgeons to improve the extent of the resection in 85% of cases. The mean duration of surgery was 390 +/- 122 minutes. Conclusion: Intraoperative MRI using a strong magnetic field (3 teslas) is a valid new technique that enables precise study of the tumor resection to determine whether the resection can be extended without damaging eloquent zones. Although the use of MRI increases the duration of surgery, the time required decreases as the team becomes more familiar with the technique. (C) 2018 SERAM. Published by Elsevier Espana, S.L.U. All rights reserved.
Revista:
JOURNAL OF TRANSLATIONAL MEDICINE
ISSN:
1479-5876
Año:
2017
Vol.:
15
N°:
1
Págs.:
Article number 104
Background: Prognosis of patients with glioblastoma multiforme (GBM) remains dismal, with median overall survival (OS) of about 15 months. It is therefore crucial to search alternative strategies that improve these results obtained with conventional treatments. In this context, immunotherapy seems to be a promising therapeutic option. We hypothesized that the addition of tumor lysate-pulsed autologous dendritic cells (DCs) vaccination to maximal safe resection followed by radiotherapy and concomitant and adjuvant temozolomide could improve patients' survival.
Methods: We conducted a phase-II clinical trial of autologous DCs vaccination in patients with newly diagnosed patients GBM who were candidates to complete or near complete resection. Candidates were finally included if residual tumor volume was lower than 1 cc on postoperative radiological examination. Autologous DCs were generated from peripheral blood monocytes and pulsed with autologous whole tumor lysate. The vaccination calendar started before radiotherapy and was continued during adjuvant chemotherapy. Progression free survival (PFS) and OS were analyzed with the Kaplan-Meier method. Immune response were assessed in blood samples obtained before each vaccines.
Results: Thirty-two consecutive patients were screened, one of which was a screening failure due to insufficient resection. Median age was 61 years (range 42-70). Karnofsky performance score (KPS) was 90-100 in 29%, 80 in 35.5% and 60-70 in 35.5% of cases. MGMT (O6-methylguanine-DNA-methyltransferase) promoter was methylated in 45.2% of patients. No severe adverse effects related to immunotherapy were registered. Median PFS was 12.7 months (CI 95% 7-16) and median OS was 23.4 months (95% CI 16-33.1). Increase in post-vaccination tumor specific immune response after vaccines (proliferation or cytokine production) was detected in 11/27 evaluated patients. No correlation between immune response and survival was found.
Conclusions: Our results suggest that the addition of tumor lysate-pulsed autologous DCs vaccination to tumor resection and combined radio-chemotherapy is feasible and safe. A multicenter randomized clinical trial is warranted to evaluate the potential survival benefit of this therapeutic approach. Trial registration This phase-II trial was registered as EudraCT: 2009-009879-35 and ClinicalTrials.gov Identifier: NCT01006044 retrospectively registered.
Autores:
Wegmann-Vicuña, R. (Autor de correspondencia); Muñoz-Hernández, D. E.; Gallegos-Constantino, V.; et al.
Revista:
ACTA OTO-LARYNGOLOGICA CASE REPORTS
ISSN:
2377-2484
Año:
2017
Vol.:
2
N°:
1
Págs.:
131 - 136
Isolated acute vestibular syndrome remains a diagnostic challenge in the emergency department and the initial approach should include the identification of a central or peripheral etiology. This is the case report of an elderly patient with known cardiovascular risk factors presenting with acute vertigo and unsteadiness. Neurological examination was notable only for down-beat nystagmus and diffusion-weighted MRI showed normal findings. He was treated as having an emerging anterior-inferior cerebellar artery (AICA) stroke. Even when MRI showed no signs of hemorrhage or infarction, the neurotological bedside examination was a determinant. The cochleovestibular system was not spared by the ischemic injury but a more extensive neurological damage was probably avoided by approaching this case as a stroke.
Revista:
PLOS ONE
ISSN:
1932-6203
Año:
2017
Vol.:
12
N°:
1
Págs.:
e0170501
Objective In this work we set to develop and to validate a new in vivo frameless orthotopic Diffuse Intrinsic Pontine Glioma (DIPG) model based in the implantation of a guide-screw system. Methods It consisted of a guide-screw also called bolt, a Hamilton syringe with a 26-gauge needle and an insulin-like 15-gauge needle. The guide screw is 2.6 mm in length and harbors a 0.5 mm central hole which accepts the needle of the Hamilton syringe avoiding a theoretical displacement during insertion. The guide-screw is fixed on the mouse skull according to the coordinates: 1 mm right to and 0.8 mm posterior to lambda. To reach the pons the Hamilton syringe is adjusted to a 6.5 mm depth using a cuff that serves as a stopper. This system allows delivering not only cells but also any kind of intratumoral chemotherapy, antibodies or gene/viral therapies. Results The guide-screw was successfully implanted in 10 immunodeficient mice and the animals were inoculated with DIPG human cell lines during the same anesthetic period. All the mice developed severe neurologic symptoms and had a median overall survival of 95 days ranging the time of death from 81 to 116 days. Histopathological analysis confirmed tumor into the pons in all animals confirming the validity of this model. Conclusion Here we presented a reproducible and frameless DIPG model that allows for rapid evaluation of tumorigenicity and efficacy of chemotherapeutic or gene therapy products delivered intratumorally to the pons.
Revista:
ACTA OTO-LARYNGOLOGICA CASE REPORTS
ISSN:
2377-2484
Año:
2017
Vol.:
3
N°:
1
Págs.:
5 - 10
Isolated vestibule-lateral semicircular canal dysplasia (LSCCD) is one of the most common inner ear malformations. We present a case of a 59-year-old patient with right vestibule-lateral canal dysplasia and a history of spontaneous vertigo spells without hearing loss. Vestibular assessment showed a dissociation between caloric responses and vestibulo-ocular reflex gain as measured with the video head-impulse test.
Revista:
NEUROPEDIATRICS
ISSN:
0174-304X
Año:
2016
Vol.:
48
N°:
1
Págs.:
53-56
There are only four previous pediatric reports of the glossopharyngeal neuralgic form of the stylohyoid complex syndrome. Stylohyoid complex has merely been described as cases of glossopharyngeal neuralgia in children. Case Report¿A 12-year-old boy came to our hospital because of recurrent episodes of severe cranial pain (9/10) lasting for 5 to 15 minutes. Pain affected the right tonsillar fossa, ear, and mastoid region. Since the start at the age of 9 years, the frequency of painful episodes has progressively increased: when admitted to our clinics 3 years later, the child was having up to five episodes daily in spite of analgesic, antiepileptic, and antidepressant drugs; he had abandoned school and leisure. Between episodes, neurological examination detected only discomfort to pressure on the right tonsillar fossa. Three-dimensional computed tomography images of the skull base showed an elongated right styloid process and bilateral calcification of the stylohyoid ligament. After surgical excision of the right styloid process and of part of the stylohyoid ligament, the glossopharyngeal painful episodes ceased. The patient remains asymptomatic seven years later. Conclusion¿In spite of its rarity in childhood, this debilitating but treatable syndrome should be kept in mind for the differential diagnosis of recurrent cranial pain in the pediatric population.
Revista:
OTOLOGY AND NEUROTOLOGY
ISSN:
1531-7129
Año:
2014
Vol.:
35
N°:
4
Págs.:
619 - 628
Hypothesis: Evaluate, based on morphologic and histologic parameters, the atraumaticity of 2 electrode arrays implanted in 10 human temporal bones.
Background: Atraumatic surgery and electrode arrays are current topics in otologic surgery. The preservation of cochlear anatomy and its functions is a priority and morphologic evaluation of the surgical trauma is essential to continue improving in this field.
Methods: Ten preserved human temporal bones (TB) without anatomic alterations were used in this study. They were divided into 2 groups of 5, and atraumatic surgery was performed to insert HiFocus 1J (group A) and HiFocus Helix (group B) electrode arrays. Anatomic comparisons were performed using computed tomography and histologic analysis.
Results: Group A: the mean length for the cochlear longitudinal axis was 10.30 mm, and the cochlear transversal axis was 7.2 mm. Scala tympani insertion was achieved in 4/5 TB studied, with a mean depth and angle of insertion of 19.2 mm and 325.5°, respectively. Lateral location of the electrode array was achieved in all specimens. No significant correlation was observed between these dimensions and depth of insertion. Group B: the mean length for the cochlear longitudinal axis was 9.52 mm, and cochlear transversal axis was 6.38 mm. Scala tympani insertion was achieved in 4/5 TB studied, with a mean depth and angle of insertion of 17.5 mm and 352°, respectively. Modiolar location of the electrode array was achieved in all specimens. A positive correlation was established between the linear and angular insertion depths (p = 0.044).
Conclusion: In summary, it is safe to state that neither electrode array shows significant insertion trauma.
Revista:
OTOLOGY AND NEUROTOLOGY
ISSN:
1531-7129
Año:
2014
Vol.:
35
N°:
4
Págs.:
619 - 628
HYPOTHESIS:
Evaluate, based on morphologic and histologic parameters, the atraumaticity of 2 electrode arrays implanted in 10 human temporal bones.
BACKGROUND:
Atraumatic surgery and electrode arrays are current topics in otologic surgery. The preservation of cochlear anatomy and its functions is a priority and morphologic evaluation of the surgical trauma is essential to continue improving in this field.
METHODS:
Ten preserved human temporal bones (TB) without anatomic alterations were used in this study. They were divided into 2 groups of 5, and atraumatic surgery was performed to insert HiFocus 1J (group A) and HiFocus Helix (group B) electrode arrays. Anatomic comparisons were performed using computed tomography and histologic analysis.
RESULTS:
Group A: the mean length for the cochlear longitudinal axis was 10.30 mm, and the cochlear transversal axis was 7.2 mm. Scala tympani insertion was achieved in 4/5 TB studied, with a mean depth and angle of insertion of 19.2 mm and 325.5°, respectively. Lateral location of the electrode array was achieved in all specimens. No significant correlation was observed between these dimensions and depth of insertion. Group B: the mean length for the cochlear longitudinal axis was 9.52 mm, and cochlear transversal axis was 6.38 mm. Scala tympani insertion was achieved in 4/5 TB studied, with a mean depth and angle of insertion of 17.5 mm and 352°, respectively. Modiolar location of the electrode array was achieved in all specimens. A positive correlation was established between the linear and angular insertion depths (p = 0.044).
CONCLUSION:
In summary, it is safe to state that neither electrode array shows significant insertion trauma.
Revista:
JOURNAL OF NEURO-ONCOLOGY
ISSN:
0167-594X
Año:
2014
Vol.:
116
N°:
1
Págs.:
169-175
Our purpose was to analyze the pattern of failure in glioblastoma (GBM) patients at first recurrence after radiotherapy and temozolomide and its relationship with different factors. From 77 consecutive GBM patients treated at our institution with fluorescence guided surgery and standard radiochemotherapy, 58 first recurrences were identified and included in a retrospective review. Clinical data including age, Karnofsky performance score, preoperative tumor volume and location, extend of resection, MGMT promoter methylation status, time to progression (PFS), overall survival (OS) and adjuvant therapies were reviewed for every patient. Recurrent tumor location respect the original lesion was the end point of the study. The recurrence pattern was local only in 65.5% of patients and non-local in 34.5%. The univariate and multivariate analysis showed that greater preoperative tumor volume in T1 gadolinium enhanced sequences, was the only variable with statistical signification (p < 0.001) for increased rate of non-local recurrences, although patients with MGMT methylation and complete resection of enhancing tumor presented non-local recurrences more frequently. PFS was longer in patients with non-local recurrences (13.8 vs. 6.4 months; p = 0.019, log-rank). However, OS was not significantly different in both groups (24.0 non-local vs. 19.3 local; p = 0.9). Rate of non-local recurrences in our series of patients treated with fluorescence guided surgery and standard radiochemotherap
Revista:
NEUROLOGY
ISSN:
0028-3878
Año:
2013
Vol.:
80
N°:
17
Págs.:
1620
A 77-year-old woman with multiple myeloma for 5 years presented with obtundation, drowsiness, and disorientation over 15 days. Complete blood count revealed thrombocytopenia (25,000/µL). A brain CT disclosed multiple extraaxial hyperdense foci without bone destruction. Differential diagnosis included tumors (meningiomas, leukemia), subdural hematomas, and intracranial hemorrhages; the lesion's multiplicity and morphology were consistent with intracranial extramedullary hematopoiesis (IEH) (figure). Despite platelet transfusions, she died 2 days later of alveolar hemorrhage. Autopsy confirmed IEH and excluded erythropoiesis, reported in subdural hematomas. The formation of blood cells outside the bone marrow is usually related to anemia or lymphoproliferative disorders and is uncommon in multiple myeloma.(1) IEH can cause seizures, hydrocephalus, or cognitive changes.(2.)
Revista:
CEPHALALGIA
ISSN:
0333-1024
Año:
2012
Vol.:
32
N°:
16
Págs.:
1220 - 1221
Revista:
ARCHIVES OF NEUROLOGY
ISSN:
0003-9942
Año:
2012
Vol.:
69
N°:
12
Págs.:
1652 - 1653
Revista:
CLINICAL IMAGING
ISSN:
0899-7071
Año:
2011
Vol.:
35
N°:
3
Págs.:
236 - 241
The 3-T fMRI shows a higher sensitivity for the motor and somatosensory stimulation and more specific localization in the grey substance. The 3-T fMRI detects additional areas of activation with the motor paradigm.
Revista:
REVISTA ESPAÑOLA DE MEDICINA NUCLEAR
ISSN:
0212-6982
Año:
2011
Vol.:
30
N°:
1
Págs.:
47-65
Revista:
REVISTA DE NEUROLOGIA
ISSN:
0210-0010
Año:
2010
Vol.:
50
N°:
7
Págs.:
441 - 442
Revista:
Cephalalgia
ISSN:
0333-1024
Año:
2010
Vol.:
30
N°:
5
Págs.:
626 - 630
Revista:
JOURNAL OF PLASTIC RECONSTRUCTIVE AND AESTHETIC SURGERY
ISSN:
1748-6815
Año:
2010
Vol.:
63
N°:
2
Págs.:
298 - 304
Revista:
GENETICS IN MEDICINE
ISSN:
1098-3600
Año:
2010
Vol.:
12
N°:
8
Págs.:
532 - 535
Revista:
JOURNAL OF NEURO-ONCOLOGY
ISSN:
0167-594X
Año:
2010
Vol.:
102
N°:
1
Págs.:
105 - 113
We analyzed the efficacy and applicability of surgery guided by 5-aminolevulinic acid (ALA) fluorescence in consecutive patients with glioblastoma multiforme (GBM). Thirty-six patients with GBM were operated on using ALA fluorescence. Resections were performed using the fluorescent light to assess the right plane of dissection. In each case, biopsies with different fluorescent quality were taken from the tumor center, from the edges, and from the surrounding tissue. These samples were analyzed separately with hematoxylin¿eosin examination and immunostaining against Ki67. Tumor volume was quantified with pre- and postoperative volumetric magnetic resonance imaging. Strong fluorescence identified solid tumor with 100% positive predictive value. Invaded tissue beyond the solid tumor mass was identified by vague fluorescence with 97% positive predictive value and 66% negative predictive value, measured against hematoxylin¿eosin examination. All the contrast-enhancing volume was resected in 83.3% of the patients, all patients had resection over 98% of the volume and mean volume resected was 99.8%. One month after surgery there was no mortality, and new or increased neurological morbidity was 8.2%. The fluorescence induced by 5-aminolevulinic can help to achieve near total resection of enhancing tumor volume in most surgical cases of GBM. It is possible during surgery to obtain separate samples of the infiltrating cells from the tumor border.
Nacionales y Regionales
Título:
Alteraciones de la sinapsis en el estriado y en la corteza frontal en la disfunción ejecutiva de la enfermedad de Parkinson
Código de expediente:
PI19/01915
Financiador:
INSTITUTO DE SALUD CARLOS III
Convocatoria:
2019 AES Proyectos de investigación
Fecha de inicio:
01/01/2020
Fecha fin:
30/06/2024
Importe concedido:
123.420,00€
Otros fondos:
Fondos FEDER
Título:
Descifrando la disociación de resultados en pruebas vestibulares de pacientes con enfermedad de Méniere unilateral
Código de expediente:
PI19/00414
Financiador:
INSTITUTO DE SALUD CARLOS III
Convocatoria:
2019 AES Proyectos de investigación
Fecha de inicio:
01/01/2020
Fecha fin:
31/12/2023
Importe concedido:
68.970,00€
Otros fondos:
Fondos FEDER
Título:
Desarrollo de técnicas de mapeado de la reactividad cerebrovascular. Aplicaciones en la cirugía de tumores cerebrales.
Código de expediente:
PI18/00084
Financiador:
INSTITUTO DE SALUD CARLOS III
Convocatoria:
AES2018 PI
Fecha de inicio:
01/01/2019
Fecha fin:
30/06/2023
Importe concedido:
62.920,00€
Otros fondos:
Fondos FEDER
Título:
Modulando el sistema inmune con adenovirus oncolíticos como estrategia para los tumores difusos de tronco (DIPGs).
Código de expediente:
PI16/00066
Investigador principal:
Marta María Alonso Roldán
Financiador:
INSTITUTO DE SALUD CARLOS III
Convocatoria:
2016 AES PROYECTOS DE INVESTIGACIÓN
Fecha de inicio:
01/01/2017
Fecha fin:
31/12/2019
Importe concedido:
86.515,00€
Otros fondos:
Fondos FEDER
Título:
Evaluación de la perfusión cerebral y la conectividad funcional en la enfermedad de Alzheimer: dos marcadores emergentes para un diagnóstico temprano
Código de expediente:
SAF2014-56330-R
Investigador principal:
María Asunción Fernández Seara
Financiador:
MINISTERIO DE CIENCIA E INNOVACIÓN
Convocatoria:
2014-MINECO Retos Investigación
Fecha de inicio:
01/01/2015
Fecha fin:
30/06/2018
Importe concedido:
90.750,00€
Otros fondos:
-