DNA methylation-based signatures classify sporadic pituitary tumors according to clinicopathological features.

BACKGROUND: Distinct genome-wide methylation patterns cluster pituitary neuroendocrine tumors (PitNETs) into molecular groups associated with specific clinicopathological features. Here we aim to identify, characterize, and validate methylation signatures that objectively classify PitNET into clinicopathological groups. METHODS: Combining in-house and publicly available data, we conducted an analysis of the methylome profile of a comprehensive cohort of 177 tumors (Panpit cohort) and 20 nontumor specimens from the pituitary gland. We also retrieved methylome data from an independent PitNET cohort (N = 86) to validate our findings. RESULTS: We identified three methylation clusters associated with adenohypophyseal cell lineages and functional status using an unsupervised approach. Differentially methylated probes (DMP) significantly distinguished the Panpit clusters and accurately assigned the samples of the validation cohort to their corresponding lineage and functional subtypes memberships. The DMPs were annotated in regulatory regions enriched with enhancer elements, associated with pathways and genes involved in pituitary cell identity, function, tumorigenesis, and invasiveness. Some DMPs correlated with genes with prognostic and therapeutic values in other intra- or extracranial tumors. CONCLUSIONS: We identified and validated methylation signatures, mainly annotated in enhancer regions that distinguished PitNETs by distinct adenohypophyseal cell lineages and functional status. These signatures provide the groundwork to develop an unbiased approach to classifying PitNETs according to the most recent classification recommended by the 2017 WHO and to explore their biological and clinical relevance in these tumors.

Mechanomyography for Intraoperative Assessment of Cortical Breach During Instrumented Spine Surgery.

OBJECTIVE: We sought to determine the utility of mechanomyography (MMG) in detecting and preventing pedicle breach in instrumented lumbar spine surgery. METHODS: In a prospective nonrandomized trial without controls, we selected consecutive patients to undergo intraoperative MMG during instrumented lumbar spine surgery. MMG testing was performed at the original pilot hole, after tapping, and after screw placement, with the minimum current to elicit a recorded MMG response. All patients underwent a postoperative computed tomography scan, and a single radiologist interpreted each pedicle to identify breach. Chi-square test was used to compare patients with and without breaches. Two sample Student's t-tests were used to compare changes in functional outcomes. Sensitivity and specificity of MMG were computed using receiver operating characteristic curve analysis. RESULTS: There were 122 consecutive instrumented lumbar surgery patients enrolled, with a total of 890 lumbar pedicle screws tested with MMG. The medial or inferior breach rate was 2.25%, with no statistically significant difference in Oswestry Disability Index or visual analog scale between patients who breached and who did not. For the MMG measurement from the original pilot hole, the area under the receiver operating characteristic was 0.835; the maximum combination of sensitivity (80.42%) and specificity (80.6%) was found using MMG current ≤12 mA. We found that an MMG cutoff of >12 mA resulted in a 99.5% likelihood of no medial or inferior breach. CONCLUSIONS: MMG can be safely used during instrumented lumbar spine surgery. A cutoff value of >12 mA for MMG can accurately predict and prevent medial and inferior pedicle screw breach.

Simple and reproducible linear measurements to determine ventricular enlargement in adults.

BACKGROUND: Recent studies have suggested that Evan's Index (EI) is not accurate and instead endorse volumetric measurements. Our aim was to evaluate the reproducibility of linear measurements and their correlation to ventricular volume. METHODS: Using magnetic resonance (MR) images of 30 patients referred for normal pressure hydrocephalus (NPH), EI, frontal-occipital horn ratio (FOR), third ventricular width and height, frontal horn width (FHW), and callosal angle (CA) at the foramen of Monro and the posterior commissure (PC) were independently measured by residents in neurosurgery and radiology, a neurosurgeon and radiologist, and a medical student. Intraclass correlation coefficients (ICC) were calculated to establish inter-rater agreement among the reviewers. Pearson's correlation coefficients were done to assess the relationship of the linear measurements with total ventricular volume. Kappa analyses were performed to assess the degree of agreement between cutpoints determined by the ROC analysis for the linear measurements and reviewers' gestalt impression about ventricular size with volumetric abnormality. RESULTS: The overall inter-rater agreement among reviewers was almost perfect for EI (ICC = 0.913), FOR (ICC = 0.830), third ventricular width, FHW (ICC = 0.88), and CA at PC (ICC = 0.865), substantial for temporal horn width (ICC = 0.729) and CA at foramen of Monro (ICC = 0.779), and moderate for third ventricular height (ICC = 0.496). EI, FOR, third ventricular width, temporal horn width, and CA at PC measures correlated with total ventricular volume. There was fair-to-almost-perfect agreement of the individual reviewer's gestalt responses of abnormatility with volumetric abnormality. Gestalt responses were better for more senior raters. CONCLUSION: Linear measurements are reliable and reproducible methods for determining ventricular enlargement.

Fibromuscular dysplasia unraveled: the pulsation-induced microtrauma and reactive hyperplasia theory.

INTRODUCTION: Fibromuscular dysplasia (FMD) is a relatively uncommon, non-inflammatory, non-atherosclerotic vascular condition of unknown etiology. There have been no major advancements in understanding FMD in the past 30-40yrs. We hypothesize that the vascular changes seen in FMD are a direct result of recurrent mechanical trauma in susceptible vessels and reflect a compensatory response to recurrent pulsation-induced mechanical trauma. METHODS: Radiology records at a large tertiary care medical center were queried for cases of cervical carotid FMD. Cases with viewable sequential angiographic evidence of FMD were selected and analyzed for degree of vessel tortuosity, FMD type, degree of vessel movement, and association with the FMD lesion. Images were independently analyzed by 1 neurologist and 2 neuroradiologists. RESULTS: Twenty-four carotid vessels in fourteen patients were identified to have FMD, 100% of patients were female, average age was 58.43±8.72yrs (range 45-73), 35.7% were black, 35.7% had HTN, 7.14% had CKD and 7.14% used tobacco in the past year. Associated findings included aneurysms and dissections. All but 1 patient had at least mild vessel tortuosity, and 28.6% were moderate or severe. All but 1 patient had at least "some" pulsation-like vessel movement, 16.7% had "significant" movement, and all movement was focally associated with the FMD abnormality. CONCLUSION: Pulsatile vascular movements were observed in high frequency and in high association with FMD. We propose a theoretical connection between the pulsation-induced movement and a process of reactive vascular hyperplasia and fibrosis responsible for the FMD phenotype and is consistent with previous findings.

Preoperative localization of parathyroid adenomas using 4-dimensional computed tomography: a pictorial essay.

Accurate preoperative localization is the key to successful parathyroid surgery in the era of minimally invasive parathyroid surgery. This article presents and discusses the embryologic basis of parathyroid gland and ectopic location and different imaging modalities helpful in diagnosing and localizing parathyroid adenomas and/or hyperplasia. We also aim to review the current surgical concepts in treatment of parathyroid adenomas and/or hyperplasia, the utility of 4-dimensional computed tomography for accurate preoperative localization of hyperfunctioning parathyroid glands, imaging classification of adenomas and/or hyperplasia, and, finally, present some of the limitations of 4-dimensional computed tomography.

Assessment of apparent diffusion coefficient in normal and degenerated intervertebral lumbar disks: initial experience.

PURPOSE: To determine prospectively the diffusibility of water in normal lumbar disks in adults by using the mean apparent diffusion coefficient (ADC) and to determine if a relationship exists between disk ADC and magnetic resonance (MR) findings of disk degeneration. MATERIALS AND METHODS: The study was approved by the Institutional Review Board, and all participants gave written informed consent prior to enrollment. Diffusion-weighted MR imaging of the lumbar spine was performed in 39 patients (all men; mean age, 53 years) and five volunteers (all men; mean age, 31 years). ADC values were recorded for each disk. All disks were visually graded by two independent observers as being normal or as showing at least one of three MR findings of degeneration on sagittal T2-weighted images. Mean ADC values of normal disks were compared with those of degenerated disks and were correlated with age and anatomic location. Data were analyzed by using Kendall correlation statistics, Mantel-Haenszel statistics, and a paired two-tailed Student t test. RESULTS: The mean ADC value was 2.27 x 10(-3) mm(2)/sec +/- 0.58 (+/- standard deviation) in normal disks and 2.06 x 10(-3) mm(2)/sec +/- 0.47 in abnormal disks (9% reduction, P = .006). A statistically significant dependence of lumbar disk ADC on anatomic location was reported (analysis of variance, P < .001), with lower ADC values seen in more caudal disks. There was no association between age and mean disk ADC. CONCLUSION: A statistically significant decrease was seen in the ADC values of degenerated lumbar disks when compared with ADC values of normal disks. More caudal disks, even when normal, showed lower ADC values than more cephalic disks.

Charcot-Marie-Tooth disease: extensive cranial nerve involvement on CT and MR imaging.

We report a case of genetically verified Charcot-Marie-Tooth disease in which the patient had cranial nerve symptoms. CT and MR imaging demonstrated enlargement of several cranial nerves, as well as their skull-base foramina, with faint contrast material enhancement identified.

Intralabyrinthine meningioma.

An 18-year-old female patient with unilateral hearing loss underwent evaluation with CT and MR imaging. A partially ossified, enhancing lesion in the bony labyrinth, with replacement of adjacent structures, was identified. Surgical biopsy revealed a meningioma arising primarily within the bony labyrinth. To our knowledge, this entity has not been previously described.