Search

Purpose: To compare logistic regression to elastic net for identifying and ranking clinical risk factors for blunt cerebrovascular injury (BCVI)., Materials and Methods: Consecutive trauma patients undergoing screening CTA at a level 1 trauma center over a 2-year period. Each internal carotid artery (ICA) and vertebral artery (VA) was independently graded by 2 neuroradiologists using the Denver grading scale. Unadjusted odds ratios were calculated by univariate and adjusted odds ratios by multiple logistic regression with FDR correction. We applied logistic regression with the elastic net penalty and tenfold cross-validation., Results: Total of 467 patients; 73 patients with BCVI. Maxillofacial fracture, basilar skull fracture, and GCS had significant unadjusted odds ratios (OR) for ICA injury and C-spine fracture, spinal ligamentous injury, and age for VA injury. Only transverse foramen fracture had significant adjusted OR for VA injury, with none for ICA injury, after FDR correction. Using elastic net, ICA injury variables included maxillofacial fracture, basilar skull fracture, GCS, and carotid canal fracture. For VA injury, these included cervical spine transverse foramen fracture, ligamentous injury, C1-C3 fractures, posterior element fracture, and vertebral body fracture., Conclusion: Elastic net statistical learning methods identified additional risk factors and outperformed multiple logistic regression for BCVI. Elastic net allows the study of a large number of variables, and is useful when covariates are correlated., (© 2021. American Society of Emergency Radiology.)

Telomerase adds telomeric repeats at chromosome ends to compensate for the telomere loss that is caused by incomplete genome end replication 1 . In humans, telomerase is upregulated during embryogenesis and in cancers, and mutations that compromise the function of telomerase result in disease 2 . A previous structure of human telomerase at a resolution of 8 Å revealed a vertebrate-specific composition and architecture 3 , comprising a catalytic core that is flexibly tethered to an H and ACA (hereafter, H/ACA) box ribonucleoprotein (RNP) lobe by telomerase RNA. High-resolution structural information is necessary to develop treatments that can effectively modulate telomerase activity as a therapeutic approach against cancers and disease. Here we used cryo-electron microscopy to determine the structure of human telomerase holoenzyme bound to telomeric DNA at sub-4 Å resolution, which reveals crucial DNA- and RNA-binding interfaces in the active site of telomerase as well as the locations of mutations that alter telomerase activity. We identified a histone H2A-H2B dimer within the holoenzyme that was bound to an essential telomerase RNA motif, which suggests a role for histones in the folding and function of telomerase RNA. Furthermore, this structure of a eukaryotic H/ACA RNP reveals the molecular recognition of conserved RNA and protein motifs, as well as interactions that are crucial for understanding the molecular pathology of many mutations that cause disease. Our findings provide the structural details of the assembly and active site of human telomerase, which paves the way for the development of therapeutic agents that target this enzyme.

OBJECTIVE. The purpose of this article was to determine whether the radiographic and CT appearance of ballistic projectiles predicts their composition and to characterize the translational, rotational, and temperature effects of a 1.5-T MRI magnetic field on representative bullets. MATERIALS AND METHODS. Commercially available handgun and shotgun ammunition representing projectiles commonly encountered in a clinical setting was fired into ballistic gelatin as a surrogate for human tissue, and radiographs and CT images of these gelatin blocks were obtained. MR images of unfired bullets suspended in gelatin blocks were also obtained using T1- and T2-weighted sequences. Magnetic attractive force, rotational torque, and heating effects of unfired bullets were assessed at 1.5 T. RESULTS. Fired bullets were separated into ferromagnetic and nonferromagnetic groups based on the presence of a debris trail and deformation of the primary projectile in the gelatin blocks. Whereas ferromagnetic bullets showed mild torque forces and marked imaging artifacts at 1.5 T, nonferromagnetic bullets did not have these effects. Heating above the Food and Drug Administration limit of 2°C was not observed in any of the projectiles tested. CONCLUSION. Patients with ballistic embedded fragments are frequently denied MRI because the bullet composition cannot be determined without shell casings. We found that radiography and CT can be used to identify nonferromagnetic projectiles that are safe for MRI. We also present an algorithm for determining the triage of patients with retained bullets.

Wiskott-Aldrich syndrome protein (WASP) activates the actin-related protein 2/3 homolog (Arp2/3) complex and regulates actin polymerization in a physiological setting. Cell division cycle 42 (Cdc42) is a key activator of WASP, which binds Cdc42 through a Cdc42/Rac-interactive binding (CRIB)-containing region that defines a subset of Cdc42 effectors. Here, using site-directed mutagenesis and binding affinity determination and kinetic assays, we report the results of an investigation into the energetic contributions of individual WASP residues to both the Cdc42-WASP binding interface and the kinetics of complex formation. Our results support the previously proposed dock-and-coalesce binding mechanism, initiated by electrostatic steering driven by WASP's basic region and followed by a coalescence phase likely driven by the conserved CRIB motif. The WASP basic region, however, appears also to play a role in the final complex, as its mutation affected both on- and off-rates, suggesting a more comprehensive physiological role for this region centered on the C-terminal triad of positive residues. These results highlight the expanding roles of the basic region in WASP and other CRIB-containing effector proteins in regulating complex cellular processes and coordinating multiple input signals. The data presented improve our understanding of the Cdc42-WASP interface and also add to the body of information available for Cdc42-effector complex formation, therapeutic targeting of which has promise for Ras-driven cancers. Our findings suggest that combining high-affinity peptide-binding sequences with short electrostatic steering sequences could increase the efficacy of peptidomimetic candidates designed to interfere with Cdc42 signaling in cancer., (© 2018 Tetley et al.)

Lumbar puncture has, for many years, been the responsibility of the internal medicine physician or the neurologist. As more patients have undergone spine surgery and with the current increase in body mass index of the general population, the radiologist has been consulted with increasing frequency to perform lumbar puncture with fluoroscopic guidance. Radiology, in fact, is now the dominant overall provider of lumbar puncture procedures. The procedure is more difficult when the needle length increases, and if fluoroscopy is used, landmarks are more difficult to visualize with increasing subcutaneous fat. Our goal with this review was to describe our techniques for lumbar puncture in the difficult patient, with emphasis on using fluoroscopy in the obese patient and to suggest maneuvers that might make the procedure easier. Combining our experience from performing these procedures on an obese population, we would like to share our tips, especially with trainees early in their career., (© 2017 by American Journal of Neuroradiology.)

Background: Posterior reversible leukoencephalopathy syndrome (PRES) is linked to various etiologies, including most importantly systemic hypertension. Its association with intracranial hypotension (IH), a potential sequela of various neurosurgical procedures, is underrecognized. We report a case of lumboperitoneal shunt-induced IH resulting in PRES with the goal to increase awareness and elaborate on the potential biologic mechanism, based on the Monro-Kellie hypothesis., Case Description: A 26-year-old woman with acquired immunodeficiency syndrome and epilepsy was admitted for recurrent cryptococcal meningitis and breakthrough seizures. There was radiologic evidence of ventricular enlargement, and opening pressure on serial lumbar punctures was constantly elevated. Owing to persistently elevated, symptomatic intracranial pressure and transient relief with serial lumbar punctures, a lumboperitoneal shunt was placed. The patient subsequently had a breakthrough seizure and became encephalopathic. Repeat head imaging showed reduced ventricular size, engorged venous sinuses, and tonsillar herniation in keeping with IH, coupled with extensive white matter abnormalities in bilateral parieto-occipital lobes indicative of PRES. The patient had an emergent programmable valve placed in the lumboperitoneal shunt to prevent excessive cerebrospinal fluid drainage, leading to clinical and radiologic improvement. Subsequent cerebrospinal fluid leak resulted in recurrent presentation., Conclusions: IH appears to be a distinct cause of PRES not previously reported in the neurosurgical literature. It occurs in susceptible patients, on average 1-5 days after the IH trigger, and seems clinically and radiologically similar to more common hypertensive cases in terms of initial presentation and prognosis. Increased vigilance is required for prompt recognition and management., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Object: The craniovertebral junction (CVJ) is unique in the spinal column regarding the degree of multiplanar mobility allowed by its bony articulations. A network of ligamentous attachments provides stability to this junction. Although ligamentous injury can be inferred on CT scans through the utilization of craniometric measurements, the disruption of these ligaments can only be visualized directly with MRI. Here, the authors review the current literature on MRI evaluation of the CVJ following trauma and present several illustrative cases to highlight the utility and limitations of craniometric measures in the context of ligamentous injury at the CVJ., Methods: A retrospective case review was conducted to identify patients with cervical spine trauma who underwent cervical MRI and subsequently required occipitocervical or atlantoaxial fusion. Craniometric measurements were performed on the CT images in these cases. An extensive PubMed/MEDLINE literature search was conducted to identify publications regarding the use of MRI in the evaluation of patients with CVJ trauma., Results: The authors identified 8 cases in which cervical MRI was performed prior to operative stabilization of the CVJ. Craniometric measures did not reliably rule out ligamentous injury, and there was significant heterogeneity in the reliability of different craniometric measurements. A review of the literature revealed several case series and descriptive studies addressing MRI in CVJ trauma. Three papers reported the inadequacy of the historical Traynelis system for identifying atlantooccipital dislocation and presented 3 alternative classification schemes with emphasis on MRI findings., Conclusions: Recognition of ligamentous instability at the CVJ is critical in directing clinical decision making regarding surgical stabilization. Craniometric measures appear unreliable, and CT alone is unable to provide direct visualization of ligamentous injury. Therefore, while the decision to obtain MR images in CVJ trauma is largely based on clinical judgment with craniometric measures used as an adjunct, a high degree of suspicion is warranted in the care of these patients as a missed ligamentous injury can have devastating consequences.

Background and Purpose: Spinal dysraphism is associated with urinary-tract dysfunction in severe cases such as meningomyelocele, in part because of incomplete innervation of the lower urinary tract. Patients with meningomyelocele are at higher risk for stone formation, possibly secondary to stasis of urine from aberrant storage and emptying. However, minimal data exist on the risk of stone formation in patients with milder forms of spinal dysraphism. The purpose of this study was to examine whether an association exists between urolithiasis and occult spinal dysraphism (OSD)., Patients and Methods: All patients who underwent a non-contrast CT scan of the abdomen and pelvis during a 4-month period were included. The final dataset consisted of 374 consecutive patients (195 men, 179 women) with a mean age of 54.2 years (range 18-95 years). Scans were reviewed for evidence of urolithiasis and, independently, for skeletal abnormalities. Patients with urolithiasis included those with a kidney, ureteral, or bladder stone(s). Patients with OSD included those with bifid lumbosacral bony elements, posterior arch defects, or incomplete fusion or non-fusion of S1, S2, or S3. The association between urolithiasis and OSD was examined by calculating series of crude and adjusted odds ratios (ORs) with corresponding 95% confidence intervals (CIs)., Results: Of the 374 patients, 135 (36.1%) had urinary calculi, and 83 (22.2%) had OSD. No relation was found between the prevalence of OSD and stone disease (OR 1.22; 95% CI 0.72, 2.08), even after adjusting for potential confounders., Conclusion: Unlike severe spinal dysraphism, OSD does not appear to confer an increased risk of stone disease.

Objective: Astroblastomas are rare glial neoplasms that usually occur in young adults and have a predilection for the cerebral hemispheres. Patients typically present with signs of increased intracranial pressure and seizures. Imaging studies reveal circumscribed, contrast-enhancing tumors that contain both cystic and solid components with variable peritumoral edema. Hemorrhage, which suggested the presence of a vascular lesion in this patient, has not been previously described as a feature of this neoplasm., Clinical Presentation: The authors report the case of a 33-year-old woman who presented with spontaneous intraparenchymal hemorrhage. The collective radiographic data suggested the presence of a cavernous malformation., Intervention: A right frontotemporal craniotomy was performed under frameless stereotactic image guidance. An astroblastoma was diagnosed after resection and neuropathological examination., Conclusion: A rare radiological to pathological correlation of astroblastoma is presented in which the evolving hematoma, as observed on magnetic resonance imaging scans, complicated the radiographic diagnosis of this lesion. The clinical, radiographic, and pathological features of astroblastomas, as well as the natural history of these rare glial neoplasms, are reviewed. This case illustrates the capacity of astroblastomas to hemorrhage, disguising the classic radiographic findings typical of this glial neoplasm.

Background and Purpose: Pulsatile tinnitus (PT), a common disorder, can be caused by a variety of otologic and vascular lesions. Various imaging modalities, including CT, MR imaging and angiography, and conventional angiography, have been used in the assessment of PT. Ideally, a single imaging study to evaluate for the largest variety of etiologies would be optimal. In our study, we examine the potential for CT arteriography and venography (CTA/V) in the evaluation of PT., Methods: Sixteen patients with PT were prospectively evaluated by an otolaryngologist, had a normal otologic examination, and were referred for a CTA/V. All examinations were performed on a 16-section multidetector CT. The carotid bifurcations, internal carotid artery course, transverse and sigmoid sinuses, jugular foramen, internal jugular vein, sella turcica, and temporal bones were evaluated., Results: Seven of the 16 patients had lesions on CTA/V that could account for their PT. Examples of pathologic conditions in the series included a significantly dominant venous system, a venous diverticulum with stricture, and a transverse sinus stenosis., Conclusions: Preliminary findings indicate that CTA/V can be a valuable imaging tool in the assessment of PT. With this technique, arterial, venous, middle, and inner ear causes of PT can be excluded.

A committee of concerned neurologists in cooperation with the Tennessee Department of Safety and other agencies reviewed the present state licensing rules for epileptics and offered recommendations for amendments. Epileptics, diabetics, and patients with cerebrovascular disease have an accident rate of approximately twice that of the general population. Seizures probably account for approximately .02% of all vehicle accidents and only .5% to .01% of the fatal accidents. Accidents caused by seizures involve the driver's vehicle alone or an immovable object 80% of the time and occur in less populated and developed areas than controls. The number of seizures within the first three months of therapy is a powerful prognostic indicator. With knowledgeable individual consideration, licensing epileptics to drive could be done much earlier than previously allowed, without affecting road safety. Physicians giving recommendations for licensing in good faith should be protected by law from liability for unforeseen seizure recurrence.