Sex Hormone Receptor Expression in Craniopharyngiomas and Association with Tumor Aggressiveness Characteristics

Craniopharyngiomas (CPs) are rare tumors of the sellar and suprasellar regions of embryonic origin. The primary treatment for CPs is surgery but it is often unsuccessful. Although CPs are considered benign tumors, they display a relatively high recurrence rate that might compromise quality of life. Previous studies have reported that CPs express sex hormone receptors, including estrogen and progesterone receptors. Here, we systematically analyzed estrogen receptor α (ERα) and progesterone receptor (PR) expression by immunohistochemistry in a well-characterized series of patients with CP (n = 41) and analyzed their potential association with tumor aggressiveness features. A substantial proportion of CPs displayed a marked expression of PR. However, most CPs expressed low levels of ERα. No major association between PR and ERα expression and clinical aggressiveness features was observed in CPs. Additionally, in our series, β-catenin accumulation was not related to tumor recurrence. View Full-TextThis work was supported by grants from the ISCIII-Subdirección General de Evaluación y Fomento de la Investigación co-funded with Fondos FEDER (PI16/00175 to A.S-M. and D.A.C.) and the Sistema Andaluz de Salud (A-0006-2017 and A-0055-2018 to A.S-M, RC-0006-2018 to D.A.C.)

In vivo cholinergic basal forebrain degeneration and cognition in Parkinson's disease: Imaging results from the COPPADIS study

COPPADIS Study Group.[Introduction] We aimed to assess associations between multimodal neuroimaging measures of cholinergic basal forebrain (CBF) integrity and cognition in Parkinson's disease (PD) without dementia.[Methods] The study included a total of 180 non-demented PD patients and 45 healthy controls, who underwent structural MRI acquisitions and standardized neurocognitive assessment through the PD-Cognitive Rating Scale (PD-CRS) within the multicentric COPPADIS-2015 study. A subset of 73 patients also had Diffusion Tensor Imaging (DTI) acquisitions. Volumetric and microstructural (mean diffusivity, MD) indices of CBF degeneration were automatically extracted using a stereotactic CBF atlas. For comparison, we also assessed multimodal indices of hippocampal degeneration. Associations between imaging measures and cognitive performance were assessed using linear models.[Results] Compared to controls, CBF volume was not significantly reduced in PD patients as a group. However, across PD patients lower CBF volume was significantly associated with lower global cognition (PD-CRStotal: r = 0.37, p < 0.001), and this association remained significant after controlling for several potential confounding variables (p = 0.004). Analysis of individual item scores showed that this association spanned executive and memory domains. No analogue cognition associations were observed for CBF MD. In covariate-controlled models, hippocampal volume was not associated with cognition in PD, but there was a significant association for hippocampal MD (p = 0.02).[Conclusions] Early cognitive deficits in PD without dementia are more closely related to structural MRI measures of CBF degeneration than hippocampal degeneration. In our multicentric imaging acquisitions, DTI-based diffusion measures in the CBF were inferior to standard volumetric assessments for capturing cognition-relevant changes in non-demented PD.This work was supported by the Alzheimer Forschung Initiative e.V. (AFI International Training Grant to MJG), the Instituto de Salud Carlos III-Fondo Europeo de Desarrollo Regional (ISCIII-FEDER) [PI14/01823, PI16/01575, PI18/01898, PI19/01576, PI20/00613], the Consejería de Economía, Innovación, Ciencia y Empleo de la Junta de Andalucía [CVI-02526, CTS-7685], the Consejería de Salud y Bienestar Social de la Junta de Andalucía [PI-0471-2013, PE-0210-2018, PI-0459-2018, PE-0186-2019], the Fundación Alicia Koplowitz and the Fundación “Curemos el Parkinson” (https://www.curemoselparkinson.org). MJG is supported by the “Miguel Servet” program [CP19/00031], MALE by the University of Seville [USE-20046-J], JFM by the “Sara Borrell” program [CD13/00229] and VI-PPIT-US from the University of Seville [USE-18817-A], SJ by the “Acción B-Clínicos-Investigadores” program [B-0007-2019], and DMG by the “Río Hortega” program [CM18/00142].Peer reviewe

In vivo cholinergic basal forebrain degeneration and cognition in Parkinson's disease: Imaging results from the COPPADIS study

Introduction: We aimed to assess associations between multimodal neuroimaging measures of cholinergic basal forebrain (CBF) integrity and cognition in Parkinson’s disease (PD) without dementia. Methods: The study included a total of 180 non-demented PD patients and 45 healthy controls, who underwent structural MRI acquisitions and standardized neurocognitive assessment through the PD-Cognitive Rating Scale (PD-CRS) within the multicentric COPPADIS-2015 study. A subset of 73 patients also had Diffusion Tensor Imaging (DTI) acquisitions. Volumetric and microstructural (mean diffusivity, MD) indices of CBF degeneration were automatically extracted using a stereotactic CBF atlas. For comparison, we also assessed multimodal indices of hippocampal degeneration. Associations between imaging measures and cognitive performance were assessed using linear models. Results: Compared to controls, CBF volume was not significantly reduced in PD patients as a group. However, across PD patients lower CBF volume was significantly associated with lower global cognition (PD-CRStotal: r =0.37, p <0.001), and this association remained significant after controlling for several potential confounding variables (p =0.004). Analysis of individual item scores showed that this association spanned executive and memory domains. No analogue cognition associations were observed for CBF MD. In covariate-controlled models, hippocampal volume was not associated with cognition in PD, but there was a significant association for hippocampal MD (p =0.02). Conclusions: Early cognitive deficits in PD without dementia are more closely related to structural MRI measures of CBF degeneration than hippocampal degeneration. In our multicentric imaging acquisitions, DTI-based diffusion measures in the CBF were inferior to standard volumetric assessments for capturing cognition- relevant changes in non-demented PD

Diagnosis of Skull Base Osteomyelitis.

Skull base osteomyelitis (SBO) is an infection of the temporal, sphenoid, or occipital bone that can be a challenge to diagnose because of its nonspecific symptoms, long clinical course, and radiologic findings that mimic those of other entities. The authors review this unusual infection on the basis of six proven cases. The diagnosis of SBO should be made according to four points: a high index of clinical suspicion, radiologic evidence of infection, repeated biopsies that are negative for malignancy, and positive results of microbiologic tests. SBO typically manifests clinically in patients with diabetes and recurrent otitis externa; the infection usually extends inferiorly to the compact bone of the infratemporal fossa, affecting the lower cranial nerve foramina. Several image-based techniques should be used to diagnose SBO. CT is the best option for evaluating bone erosion and demineralization, MRI can help delineate the anatomic location and extent of disease, and nuclear imaging is useful for confirming bone infection with high sensitivity. However, the standard diagnostic procedure for SBO is for patients to undergo repeated biopsies to rule out malignancy, with histopathologic signs of infection and detection of microorganisms in the biopsied bone or soft tissue indicating SBO. The ability to diagnose SBO can be increased by identifying patients at risk, recognizing the most important causes and routes of infection, describing the main radiologic findings, and always considering the differential diagnosis. ©RSNA, 2021

Neuro-Behçet: Pons Involvement with Longitudinal Extension to Midbrain and Hypertrophic Olivary Degeneration

A 21-year-old right-handed man developed progressive dysarthria and gait disturbance over 4 months (associated with intermittent hiccups). During that time, he also suffered from uveitis. A physical examination showed pseudobulbar and pyramidal signs and genital and oral ulcers. A brain MRI revealed an extensive lesion mainly located in the ventral pons, with an extension upwards to the midbrain. The inferior olivary nucleus also showed hyperintensity. After the treatment with intravenous methylprednisolone and pulses of cyclophosphamide, he improved. As observed on his MRI, his lesions also improved, except for an increase of the inferior olivary nucleus, consistent with hypertrophic olivary degeneration. Neuro-Behçet tropism for ventral brainstem explains the usual presentation with pyramidal syndrome. Hypertrophic olivary degeneration due to pons involvement could explain the hiccup attacks in a few known cases

3D Printing of Diffuse Low-Grade Gliomas Involving Eloquent Cortical Areas and Subcortical Functional Pathways: Technical Note

[Background] Surgical resection of diffuse low-grade gliomas (DLGGs) involving cortical eloquent areas and subcortical functional pathways represents a challenge in neurosurgery. Patient-specific, 3-dimensional (3D)-printed models of head and brain structures have emerged in recent years as an educational and clinical tool for patients, doctors, and surgical residents.[Methods] Using multimodal high-definition magnetic resonance imaging data, which incorporates information from specific task-based functional neuroimaging and diffusion tensor imaging tractography and rapid prototyping technologies with specialized software and “in-house” 3D printing, we were able to generate 3D-printed head models that were used for preoperative patient education and consultation, surgical planning, and resident training in 2 complicated DLGG surgeries.[Results] This 3D-printed model is rapid prototyped and shows a means to model individualized, diffuse, low-level glioma in 3D space with respect to cortical eloquent areas and subcortical pathways. Survey results from 8 surgeons with different levels of expertise strongly support the use of this model for surgical planning, intraoperative surgical guidance, doctor-patient communication, and surgical training (>95% acceptance).[Conclusions] Spatial proximity of DLGG to cortical eloquent areas and subcortical tracts can be readily assessed in patient-specific 3D printed models with high fidelity. 3D-printed multimodal models could be helpful in preoperative patient consultation, surgical planning, and resident training.Funding for this technical paper was received from the Instituto de Salud Carlos III-Fondo Europeo de Desarrollo Regional (PI14/01823, PI16/01575, PI18/01898, PI19/01576), Consejería de Economía, Innovación, Ciencia y Empleo de la Junta de Andalucía (CVI-02526, CTS-7685), Consejería de Salud y Bienestar Social de la Junta de Andalucía (PI-0471–2013, PE-0210–2018, PI-0459–2018, PE-0186–2019), the Fundación Alicia Koplowitz and the Spanish Ministry of Science and Innovation “Retos Colaboración” 2019 program (TC2019–007150–1). Jose Gomez-Feria Ferreiro is supported by the Spanish Ministry of Education, Culture and Sports (FPU16/03550). The Hospital Virgen del Rocío Fabrication Laboratory is partially funded by (PIN-0213–2018) 3D printing Laboratory for Andalusian Public Health Service. Juan F Martín-Rodríguez is supported by the VI-PPIT-US from the University of Seville (USE-18817-A).Peer reviewe

Nuestra experiencia en prolactinomas mayores de 60 mm

[EN] Introduction: Giant prolactinomas (tumor size larger than 40 mm) are a rare entity of benign nature. Prolactinomas larger than 60 mm are usually underrepresented in published studies and their clinical presentation, outcomes and management might be different from smaller giant prolactinomas. Patients and methods: We retrospective collected data from patients with prolactinomas larger than 60 mm in maximum diameter and prolactin (PRL) serum levels higher than 21,200 μIU/mL in our series of prolactinomas (283). Data were collected from January 2012 to December 2017. We included three patients with prolactinomas larger than 60 mm. Results: At diagnosis, two patients presented neurological symptoms and one nasal protrusion. All patients received medical treatment with dopamine agonists. No surgical procedure was performed. Median prolactin levels at diagnosis was 108,180 [52,594–514,984] μIU/mL. Medical treatment achieved a marked reduction (>99%) in prolactin levels in all cases. Tumor size reduction (higher than 33%) was observed in all cases. In one patient cerebrospinal fluid (CSF) leak was observed after tumor shrinkage. Conclusions: Dopamine agonists appear to be an effective and safe first-line treatment in prolactinomas larger than 60 mm even in life-threatening situations. More studies with a higher number of patients are necessary to obtain enough data to make major recommendations.[ES] Introducción: Los prolactinomas gigantes (de tamaño superior a 40 mm) son una entidad rara de naturaleza benigna. Los prolactinomas mayores de 60 mm suelen estar infrarrepresentados en los estudios publicados, y su presentación clínica, resultados y tratamiento podrían ser diferentes de los de prolactinomas gigantes más pequeños. Pacientes y métodos: Recogimos retrospectivamente datos de pacientes con prolactinomas de más de 60 mm de diámetro máximo y con concentraciones séricas de prolactina (PRL) superiores a 21.200 μIU/ml de nuestra serie de prolactinomas (283). Los datos se recogieron entre enero de 2012 y diciembre de 2017. Se incluyeron 3 pacientes con prolactinomas mayores de 60 mm. Resultados: En el momento del diagnóstico, 2 pacientes presentaban síntomas neurológicos, y uno protrusión nasal. Todos los pacientes recibieron tratamiento médico con agonistas dopaminérgicos. No se realizó ninguna intervención quirúrgica. La mediana de las concentraciones de PRL al diagnóstico fue de 108.180 (52.594-514.984) μIU/ml. El tratamiento médico logró una reducción notable (> 99%) de los valores de prolactina en todos los casos. En todos los casos se observó una reducción del tamaño del tumor (superior al 33%). En un paciente se observó una fuga de líquido cefalorraquídeo (LCR) tras la reducción del tumor. Conclusión: Los agonistas dopaminérgicos parecen ser un tratamiento de primera línea eficaz y seguro en los prolactinomas mayores de 60 mm incluso en situaciones peligrosas para la vida. Se necesitan más estudios con un mayor número de pacientes para obtener datos suficientes para hacer recomendaciones importantes

Effect of age at onset on cortical thickness and cognition in posterior cortical atrophy.

Age at onset (AAO) has been shown to influence the phenotype of Alzheimer's disease (AD), but how it affects atypical presentations of AD remains unknown. Posterior cortical atrophy (PCA) is the most common form of atypical AD. In this study, we aimed to investigate the effect of AAO on cortical thickness and cognitive function in 98 PCA patients. We used Freesurfer (v5.3.0) to compare cortical thickness with AAO both as a continuous variable, and by dichotomizing the groups based on median age (58&nbsp;years). In both the continuous and dichotomized analyses, we found a pattern suggestive of thinner cortex in precuneus and parietal areas in earlier-onset PCA, and lower cortical thickness in anterior cingulate and prefrontal cortex in later-onset PCA. These cortical thickness differences between PCA subgroups were consistent with earlier-onset PCA patients performing worse on cognitive tests involving parietal functions. Our results provide a suggestion that AAO may not only affect the clinico-anatomical characteristics in AD but may also affect atrophy patterns and cognition within atypical AD phenotypes