The Cortico-Limbo-Thalamo-Cortical Circuits: An Update to the Original Papez Circuit of the Human Limbic System

The Papez circuit, first proposed by James Papez in 1937, is a circuit believed to control memory and emotions, composed of the cingulate cortex, entorhinal cortex, parahippocampal gyrus, hippocampus, hypothalamus, and thalamus. Pursuant to James Papez, Paul Yakovlev and Paul MacLean incorporated the prefrontal/orbitofrontal cortex, septum, amygdalae, and anterior temporal lobes into the limbic system. Over the past few years, diffusion-weighted tractography techniques revealed additional limbic fiber connectivity, which incorporates multiple circuits to the already known complex limbic network. In the current review, we aimed to comprehensively summarize the anatomy of the limbic system and elaborate on the anatomical connectivity of the limbic circuits based on the published literature as an update to the original Papez circuit

IDH1 prR32H CtDNA and D-2-Hydroxyglutarate as CSF Biomarkers in Patients With IDH-Mutant Gliomas

INTRODUCTION: We aimed to evaluate IDH1 p.R132H mutation and 2-hydroxyglutarate (2HG) in cerebrospinal fluid (CSF) as biomarkers for patients with IDH-mutant gliomas. METHODS: CSF was collected from patients with infiltrating glioma, and 2HG levels were measured by liquid chromatography-mass spectrometry. IDH1 p.R132H mutant allele frequency (MAF) in CSF-ctDNA was measured by digital droplet PCR (ddPCR). Tumor volume was measured from standard-of-care magnetic resonance images. RESULTS: The study included 48 patients, 6 with IDH-mutant and 42 with IDH-wildtype gliomas, and 57 samples, 9 from the patients with IDH-mutant and 48 from the patients with IDH-wildtype gliomas. ctDNA was detected in 7 of the 9 samples from patients with IDH-mutant glioma, and IDH1 p.R132H mutation was detected in 5 of the 7 samples. The MAF ranged from 0.3 to 39.95%. Total 2HG level, D-2HG level, and D/L-2HG ratio in CSF were significantly higher in patients with IDH-mutant gliomas than in patients with IDH-wildtype gliomas. D-2HG level and D/L-2HG ratio correlated with total tumor volume in patients with IDH-mutant gliomas but not in patients with IDH-wildtype gliomas. CONCLUSION: Our results suggest that detection of IDH1 p.R132H mutation by ddPCR and increased D-2HG level in CSF may help identify IDH-mutant gliomas. Our results also suggest that D-2HG level and D/L-2HG ratio correlate with tumor volume in patients with IDH-mutant gliomas. Further prospective studies with larger cohorts are needed to validate these findings

The Impact of 6 and 12 Months in Space on Human Brain Structure and Intracranial Fluid Shifts

As plans develop for Mars missions, it is important to understand how long-duration spaceflight impacts brain health. Here we report how 12-month (n = 2 astronauts) versus 6-month (n = 10 astronauts) missions impact brain structure and fluid shifts. We collected MRI scans once before flight and four times after flight. Astronauts served as their own controls; we evaluated pre- to postflight changes and return toward preflight levels across the 4 postflight points. We also provide data to illustrate typical brain changes over 7 years in a reference dataset. Twelve months in space generally resulted in larger changes across multiple brain areas compared with 6-month missions and aging, particularly for fluid shifts. The majority of changes returned to preflight levels by 6 months after flight. Ventricular volume substantially increased for 1 of the 12-month astronauts (left: +25%, right: +23%) and the 6-month astronauts (left: 17 ± 12%, right: 24 ± 6%) and exhibited little recovery at 6 months. Several changes correlated with past flight experience; those with less time between subsequent missions had larger preflight ventricles and smaller ventricular volume increases with flight. This suggests that spaceflight-induced ventricular changes may endure for long periods after flight. These results provide insight into brain changes that occur with longduration spaceflight and demonstrate the need for closer study of fluid shift

Hybrid computed tomography and magnetic resonance imaging 3D printed models for neurosurgery planning

In the last decade, the clinical applications of three-dimensional (3D) printed models, in the neurosurgery field among others, have expanded widely based on several technical improvements in 3D printers, an increased variety of materials, but especially in postprocessing software. More commonly, physical models are obtained from a unique imaging technique with potential utilization in presurgical planning, generation/creation of patient-specific surgical material and personalized prosthesis or implants. Using specific software solutions, it is possible to obtain a more accurate segmentation of different anatomical and pathological structures and a more precise registration between different medical image sources allowing generating hybrid computed tomography (CT) and magnetic resonance imaging (MRI) 3D printed models. The need of neurosurgeons for a better understanding of the complex anatomy of central nervous system (CNS) and spine is pushing the use of these hybrid models, which are able to combine morphological information from CT and MRI, and also able to add physiological data from advanced MRI sequences, such as diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI), perfusion weighted imaging (PWI) and functional MRI (fMRI). The inclusion of physiopathological data from advanced MRI sequences enables neurosurgeons to identify those areas with increased biological aggressiveness within a certain lesion prior to surgery or biopsy procedures. Preliminary data support the use of this more accurate presurgical perspective, to select the better surgical approach, reduce the global length of surgery and minimize the rate of intraoperative complications, morbidities or patient recovery times after surgery. The use of 3D printed models in neurosurgery has also demonstrated to be a valid tool for surgeons training and to improve communication between specialists and patients. Further studies are needed to test the feasibility of this novel approach in common clinical practice and determine the degree of improvement the neurosurgeons receive and the potential impact on patient outcome.This work has been partially funded by the Ministry of Science, Innovation and Universities of the Government of Spain, through the Torres Quevedo program under grant PTQ-16-08419

Preflight, In-Flight, and Postflight Imaging of the Cervical and Lumbar Spine in Astronauts.

BACKGROUND: Back pain is a common complaint during spaceflight that is commonly attributed to intervertebral disc swelling in microgravity. Ultrasound (US) represents the only imaging modality on the International Space Station (ISS) to assess its etiology. The present study investigated: 1) The agreement and correlation of spinal US assessments as compared to results of pre- and postflight MRI studies; and 2) the trend in intervertebral disc characteristics over the course of spaceflight to ISS. METHODS: Seven ISS astronauts underwent pre- and postflight US examinations that included anterior disc height and anterior intervertebral angles with comparison to pre- and postflight MRI results. In-flight US images were analyzed for changes in disc height and angle. Statistical analysis included repeated measures ANOVA with Bonferroni post hoc analysis, Bland-Altman plots, and Pearson correlation. RESULTS: Bland-Altman plots revealed significant disagreement between disc heights and angles for MRI and US measurements while significant Pearson correlations were found in MRI and US measurements for lumbar disc height (r2 = 0.83) and angle (r2 = 0.89), but not for cervical disc height (r2 = 0.26) or angle (r2 = 0.02). Changes in anterior intervertebral disc angle-initially increases followed by decreases-were observed in the lumbar and cervical spine over the course of the long-duration mission. The cervical spine demonstrated a loss of total disc height during in-flight assessments (∼0.5 cm). DISCUSSION: Significant disagreement but significant correlation was noted between US and MRI measurements of disc height and angle. Consistency in imaging modality is important for trending measurements and more research related to US technique is required.Harrison MF, Garcia KM, Sargsyan AE, Ebert D, Riascos-Castaneda RF, Dulchavsky SA. Preflight, in-flight, and postflight imaging of the cervical and lumbar spine in astronauts. Aerosp Med Hum Perform. 2018; 89(1):32-40

Preflight, in-flight, and postflight imaging of the cervical and lumbar spine in astronauts

BACKGROUND: Back pain is a common complaint during spaceflight that is commonly attributed to intervertebral disc swelling in microgravity. Ultrasound (US) represents the only imaging modality on the International Space Station (ISS) to assess its etiology. The present study investigated: 1) The agreement and correlation of spinal US assessments as compared to results of pre- and postflight MRI studies; and 2) the trend in intervertebral disc characteristics over the course of spaceflight to ISS. METHODS: Seven ISS astronauts underwent pre- and postflight US examinations that included anterior disc height and anterior intervertebral angles with comparison to pre- and postflight MRI results. In-flight US images were analyzed for changes in disc height and angle. Statistical analysis included repeated measures ANOVA with Bonferroni post hoc analysis, Bland-Altman plots, and Pearson correlation. RESULTS: Bland-Altman plots revealed significant disagreement between disc heights and angles for MRI and US measurements while significant Pearson correlations were found in MRI and US measurements for lumbar disc height (r2 = 0.83) and angle (r2 = 0.89), but not for cervical disc height (r2 = 0.26) or angle (r2 = 0.02). Changes in anterior intervertebral disc angle-initially increases followed by decreases-were observed in the lumbar and cervical spine over the course of the long-duration mission. The cervical spine demonstrated a loss of total disc height during in-flight assessments (∼0.5 cm). DISCUSSION: Significant disagreement but significant correlation was noted between US and MRI measurements of disc height and angle. Consistency in imaging modality is important for trending measurements and more research related to US technique is required.Harrison MF, Garcia KM, Sargsyan AE, Ebert D, Riascos-Castaneda RF, Dulchavsky SA. Preflight, in-flight, and postflight imaging of the cervical and lumbar spine in astronauts. Aerosp Med Hum Perform. 2018; 89(1):32-40

Dural metastasis: An uncommon form of recurrence in malignant sinonasal tumours

Presentamos las metástasis durales como forma inusual de diseminación de tumores nasosinusales malignos tratados; se revisan 20 casos diagnosticados durante el seguimiento imagenológico a un grupo tratado con resección craneofacial anterior. Evaluamos metástasis durales en 12 carcinomas nasosinusales indiferenciados, 7 neuroblastomas olfatorios y un carcinoma adenoquístico. En neuroblastomas olfatorios aparecieron metástasis durales en promedio 7,3 años postratamiento. La distancia máxima del tumor a la metástasis fue de 14 cm para neuroblastoma olfatorio y de 4,3 cm para carcinoma nasosinusal indiferenciado. Observamos metástasis durales en los agujeros de trepanación en el 50% de los carcinomas nasosinusales indiferenciados y en el 29% de los neuroblastomas olfatorios. Las metástasis durales presentaron patrón nodular (60%), multinodular (10%), quístico (15%) y en placa (15%). Proponemos un mecanismo venoso local de diseminación relacionado a disrupción tumoral o quirúrgica de la fosa craneal anterior. El seguimiento a largo plazo con inclusión craneal estaría indicado por la posible presentación tardía y distante de metástasis durales.Dural metastases are an unusual form of spread in treated sinonasal malignancies. An analysis is presented of 20 cases of dural metastases diagnosed during imaging follow-up in a selection of cases in which anterior craniofacial resection was performed. They included 12 undifferentiated sinonasal carcinomas, 7 olfactory neuroblastomas, and 1 adenoid cystic carcinoma case. Dural metastases appeared on an average of 7.3 years after treatment in olfactory neuroblastoma. The maximum distance from malignancy to dural metastases was 14 cm for olfactory neuroblastoma, and 4.3 cm for undifferentiated sinonasal carcinoma. Dural metastases in the Burr holes were observed in 50% of undifferentiated sinonasal carcinoma, and 29% of olfactory neuroblastomas. Dural metastases presented as a nodular (60%), multinodular (10%), cystic (15%), and plaque (15%) pattern. These are suggestive of a local venous spread mechanism related to tumour rupture during surgery of anterior cranial fossa. Long-term follow-up with cranial inclusion would be indicated, given the possible late and distant presentation of dural metastases

Diffusion Tensor Imaging of Human Cerebellar Pathways and their Interplay with Cerebral Macrostructure

Cerebellar white matter connections to the central nervous system are classified functionally into the spinocerebellar, vestibulocerebellar, and cerebrocerebellar subdivisions. The Spinocerebellar (SC) pathways project from spinal cord to cerebellum, whereas the vestibulocerebellar (VC) pathways project from vestibular organs of the inner ear. Cerebrocerebellar connections are composed of feed forward and feedback connections between cerebrum and cerebellum including the cortico-ponto-cerebellar (CPC) pathways being of cortical origin and the dentate-rubro-thalamo-cortical (DRTC) pathway being of cerebellar origin. In this study we systematically quantified the whole cerebellar system connections using diffusion tensor magnetic resonance imaging (DT-MRI). Ten right-handed healthy subjects (7 males and 3 females, age range 20-51 years) were studied. DT-MRI data were acquired with a voxel size = 2mm x 2mm x 2 mm at a 3.0 Tesla clinical MRI scanner. The DT-MRI data were prepared and analyzed using anatomically-guided deterministic tractography methods to reconstruct the SC, DRTC, fronto-ponto-cerebellar (FPC), parieto-ponto-cerebellar (PPC), temporo-ponto-cerebellar (TPC) and occipito-ponto-cerebellar (OPC). The DTI-attributes or the cerebellar tracts along with their cortical representation (Brodmann areas) were presented in standard Montréal Neurological Institute space. All cerebellar tract volumes were quantified and correlated with volumes of cerebral cortical, subcortical gray matter (GM), cerebral white matter (WM) and cerebellar GM, and cerebellar WM. On our healthy cohort, the ratio of total cerebellar GM-to-WM was ~ 3.29 ± 0.24, whereas the ratio of cerebral GM-to-WM was approximately 1.10 ± 0.11. The sum of all cerebellar tract volumes is ~ 25.8 ± 7.3 mL, or a percentage of 1.52 ± 0.43 of the total intracranial volume