Imaging of pediatric skull lytic lesions: A review.

Skull lesions in pediatric population are common findings on imaging and sometimes with heterogeneous manifestations, constituting a diagnostic challenge. Some lesions can be misinterpreted for their aggressiveness, as with larger lesions eroding cortical bone, containing soft tissue components, leading to excessive and, in some cases, invasive inappropriate etiological investigation. In this review, we present multiple several conditions that may present as skull lesions or pseudolesions, organized by groups (anatomic variants, congenital and development disorders, traumatic injuries, vascular issues, infectious conditions, and tumoral processes). Anatomic variants are common imaging findings that must be recognized by the neuroradiologist. Congenital malformations are rare conditions, such as aplasia cutis congenita and sinus pericranii, usually seen at earlier ages, the majority of which are benign findings. In case of trauma, cephalohematoma, growing skull fractures, and posttraumatic lytic lesions should be considered. Osteomyelitis tends to be locally aggressive and may mimic malignancy, in which cases, the clinical history can be the key to diagnosis. Vascular (sickle cell disease) and tumoral (aneurismal bone cyst, eosinophilic granuloma, metastases) lesions are relatively rare lesions but should be considered in the differential diagnosis, in the presence of certain imaging findings. The main difficulty is the differentiation between the benign and malignant nature; therefore, the main objective of this pictorial essay is to review the main skull lytic lesions found in pediatric age, describing the main findings in different imaging modalities (CT and MRI), allowing the neuroradiologist greater confidence in establishing the differential diagnosis, through a systematic and simple characterization of the lesions.

Aseptic leptomeningitis induced by azathioprine in systemic lupus erythematosus: a rare manifestation.

Systemic lupus erythematosus (SLE) is an autoimmune systemic disease and these patients can have neurological involvement; however, aseptic leptomeningitis is considered to be a very rare feature, observed in 1.4-2.0% of patients. Here, we described a case of a young male with SLE treated with azathioprine with progressive headache, which revealed diffuse posterior fossa leptomeningitis, relatively sparing the supratentorial compartment, that represent an adverse drug reaction - a rare manifestation of central nervous system involvement in SLE. Treatment with azathioprine was interrupted and methylprednisolone was initiated and the patient has significant improvement of his neurological state in 5 days later, demonstrating total involution of the leptomeningeal enhancement on MRI follow-up.

Unusual Spinal Foraminal Hemangioblastoma With Prominent Arteriovenous Shunt.

Von Hippel-Lindau (VHL) disease is a rare neurocutaneous disorder characterized by multiple benign and malignant tumors involving different organs (renal, adrenal, pancreas, liver, urogenital system, central nervous system, and head and neck region) due to mutations in the VHL tumor suppressor gene. Here, we describe a patient with unknown VHL disease who has complained of hypoesthesia of the right lower limb for about six years. A lumbar MRI was performed and revealed an expansive foraminal lesion at the right L3-L4 level and multiple serpiginous intradural and extramedullary flow voids involving the dorsal aspect of the spinal cord. The patient underwent digital subtraction angiography to exclude a spinal dural arteriovenous fistula, which revealed imaging features suggestive of spinal hemangioblastoma. In the presence of a spinal hemangioblastoma, a brain MRI was performed for further evaluation to rule out the possible diagnosis of VHL disease, and a solitary hemangioblastoma on the right cerebellar hemisphere was found. The patient underwent lumbar spine surgery, confirming the suspicious diagnosis of hemangioblastomas related to VHL disease.

Case Report: Evolutionary Clinical-Radiological Features of a Diffuse Hemispheric Glioma, H3 G34 Mutant with Over 5 Years of Survival.

Diffuse hemispheric glioma (DHG), H3 G34 mutant was included in the 5th edition of the World Health Organization Classification of Tumors of the Central Nervous System recently published. Given the recent inclusion in the current classification and its rarity in adult patients, there are scarce data on clinical-radiological characteristics, survival, and outcome. The authors report the case of a 35-year-old female with DHG, H3 G34-mutant characteristics and outcomes with an unusual presentation, recurrence, and prolonged survival. In conclusion, our case report demonstrates relevant details that should be observed in patients with suspicion or confirmation of the diagnosis of DHG, H3 G34 mutant, not only in the initial presentation but also in the evolution to ensure more personalized treatment.

Intracranial vessel wall magnetic resonance imaging features of infectious vasculitis.

Vasculitis is a complication of several infectious diseases affecting the central nervous system, which may result in ischemic and/or hemorrhagic stroke, transient ischemic attack, and aneurysm formation. The infectious agent may directly infect the endothelium, causing vasculitis, or indirectly affect the vessel wall through an immunological mechanism. The clinical manifestations of these complications usually overlap with those of non-infectious vascular diseases, making diagnosis challenging. Intracranial vessel wall magnetic resonance imaging (VWI) enables the evaluation of the vessel wall and the diseases that affect it, providing diagnostic data beyond luminal changes and enabling the identification of inflammatory changes in cerebral vasculitis. This technique demonstrates concentric vessel wall thickening and gadolinium enhancement, associated or not with adjacent brain parenchymal enhancement, in patients with vasculitis of any origin. It permits the detection of early alterations, even before a stenosis occurs. In this article, we review the intracranial vessel wall imaging features of infectious vasculitis of bacterial, viral, and fungal etiologies.

Arterial Spin Labeling: Techniques, Clinical Applications, and Interpretation.

Arterial spin labeling (ASL) is an emerging noninvasive MRI technique for assessing cerebral perfusion. An important advantage of ASL perfusion is the lack of a requirement for an exogenous tracer. ASL uses magnetically labeled water protons from arterial blood as an endogenous diffusible tracer. For this reason, ASL is an attractive perfusion imaging modality for children and for patients with contraindications or adverse reactions to gadolinium, patients with renal failure, and those who need repeated follow-up imaging. Another advantage of ASL is the possibility of quantifying cerebral blood flow, which provides an opportunity for comparative analysis among multiple longitudinal studies, unlike other MR perfusion techniques, which are semiquantitative and yield relative perfusion parameters. Advances in MRI technology and pulse sequence design have translated ASL beyond the research arena to successful clinical implementation. However, ASL is still underused in routine clinical practice. Some disadvantages of ASL include a lower signal-to-noise ratio and a longer acquisition time than those with dynamic susceptibility contrast-enhanced MRI. Additional factors limiting the use of ASL include variations in existing techniques and pulse sequence design, the complexity of implementation and postprocessing, insufficient experience with and/or knowledge of the potential clinical applications, and the absence of interpretation guidelines. The authors review the technical and physiologic basis of ASL perfusion, as well as artifacts, pitfalls, and its current clinical applications. A practical approach for interpreting ASL findings is also suggested.

Rituximab pharmacokinetic and pharmacokinetic-pharmacodynamic evaluation based on a study in diffuse large B-cell lymphoma: Influence of tumor size on pharmacokinetic and assessment of pharmacokinetic similarity.

Dr. Reddy's Laboratories rituximab (DRL_RI; Dr. Reddy's Laboratories SA, Basel, Switzerland) is under development as a rituximab biosimilar. Study RI-01-002 (Clinical Trials Registry - India/2012/11/003129), comparing DRL_RI to the reference medicinal product (RMP) MabThera® (Roche, Grenzach-Wyhlen, Germany), demonstrated pharmacokinetic (PK) equivalence and showed comparable pharmacodynamic, efficacy, safety, and immunogenicity profiles. We used data from the same study to perform population PK and PK-pharmacodynamic analyses: first exploring possible factors influencing the PK similarity assessment between products and then performing simulations to investigate the impact of tumor size on rituximab PK. Nonlinear mixed-effects models for PK, tumor size, tumor size-PK, and tumor response were developed independently. The final PK model included drug product as a dose-scaling parameter and predicted a 6.75% higher dose reaching the system in RMP-treated patients. However, when tumor size was included in the tumor size-PK model, the drug product effect was no longer observed. The model rather indicated that patients with larger tumor size have higher clearance. Further simulations confirmed that higher baseline tumor size is associated to slightly lower rituximab exposure. Tumor response, described by a continuous-time Markov model, did not differ between drug products. Both had higher effects during the first 20 weeks of treatment. Also, the model described a subpopulation of nonresponders to treatment (42%) with faster transitions to a worse state. The different rituximab exposure initially detected between drug products (6.75%) was shown using PK/PK-pharmacodynamic analysis to be attributed to a tumor size imbalance between treatment groups. PK/PK-pharmacodynamic analyses may contribute to PK similarity assessments.

Neurosyphilis and High-Resolution Vessel Wall Imaging: A Powerful Tool to Detect Vasculitis and Neuritis.

Syphilis is a reemergent infection worldwide. There has been a steady increase in incidence across many population groups in the last decades, requiring public health authorities' attention. We report a case of a 67-year-old man with neurosyphilis who presented with abrupt clinical ophthalmic changes and sensorineural hearing loss. The neuroradiological investigation demonstrated cranial nerves and vascular involvement, detected on high-resolution vessel wall imaging in brain magnetic resonance imaging. CSF and blood VDRL test were positive, as well as blood serum fluorescent treponemal antibody absorption test (FTA-ABS) and chemiluminescent magnetic microparticle immunoassay (CMIA). A test for the human immunodeficiency virus was negative. The patient was administered intravenous penicillin G for 21 days and was discharged well, with no neurologic signs.

Cervical solitary fibrous tumor: case report and literature review.

Solitary fibrous tumors (SFTs) are rare neoplasms in the spinal canal. There are few studies addressing SFT/hemangiopericytomas with no distinctive clinical characteristics, no conclusive radiological findings or even a well-defined best treatment strategy. We described a rare case of cervical SFT/hemangiopericytomas in a young patient with spinal cord compression. There are many differential diagnoses for spinal dural-based masses of which meningiomas are the most common. Surgeons and oncologists should be aware of differentials of dural-based masses in the spinal cord for surgical decision making and to guide treatment.

Myxoid glioneuronal tumour - report of three cases of a new tumour in a typical location and review of literature.

Formerly called dysembryoplastic neuroepithelial tumour (DNET) of the septum pellucidum, myxoid glioneuronal tumour (MGT) was recently recognized as a distinct entity. We report three cases of presumed MGT with typical location and image features.

Current uses of intracranial vessel wall imaging for clinical practice: a high-resolution MR technique recently available.

Intracranial vessel wall imaging plays an increasing role in diagnosing intracranial vascular diseases. With the growing demand and subsequent increased use of this technique in clinical practice, radiologists and neurologists should be aware of the choices in imaging parameters and how they affect image quality, clinical indications, methods of assessment, and limitations in the interpretation of these images. Due to the improvement of the MRI techniques, the possibility of accurate and direct evaluation of the abnormalities in the arterial vascular wall (vessel wall imaging) has evolved, adding substantial data to diagnosis when compared to the indirect evaluation based on conventional flow analyses. Herein, the authors proposed a comprehensive approach of this technique reinforcing appropriated clinical settings to better use intracranial vessel wall imaging.

Current uses of intracranial vessel wall imaging for clinical practice: a high-resolution MR technique recently available / Usos atuais do estudo de parede vascular intracraniana na prática clínica: uma técnica de RM de alta resolução recentemente disponível

ABSTRACT Intracranial vessel wall imaging plays an increasing role in diagnosing intracranial vascular diseases. With the growing demand and subsequent increased use of this technique in clinical practice, radiologists and neurologists should be aware of the choices in imaging parameters and how they affect image quality, clinical indications, methods of assessment, and limitations in the interpretation of these images. Due to the improvement of the MRI techniques, the possibility of accurate and direct evaluation of the abnormalities in the arterial vascular wall (vessel wall imaging) has evolved, adding substantial data to diagnosis when compared to the indirect evaluation based on conventional flow analyses. Herein, the authors proposed a comprehensive approach of this technique reinforcing appropriated clinical settings to better use intracranial vessel wall imaging.

RESUMO O estudo angiográfico intracraniano não invasivo está sendo amplamente utilizado no diagnóstico de doenças vasculares intracranianas. Com a crescente demanda e o aumento subsequente do uso dessa técnica na prática clínica, radiologistas e neurologistas devem estar cientes das opções nos parâmetros de imagem e como estes afetam a qualidade da imagem, as indicações clínicas, os métodos de avaliação e as limitações na interpretação dessas imagens. Devido ao aprimoramento das técnicas de imagem por RM, a possibilidade de avaliação precisa e direta das anormalidades na parede vascular arterial (vessel wall imaging) evoluiu, agregando dados substanciais ao diagnóstico quando comparados à avaliação indireta baseada em análises de fluxo convencionais. Neste artigo, os autores discorrem sobre a avaliação e interpretação dos achados de imagem desta nova técnica e suas aplicações clínicas.

Pharmacokinetic Similarity and Comparative Pharmacodynamics, Safety, Efficacy, and Immunogenicity of DRL_RI Versus Reference Rituximab in Biologics-Naïve Patients with Moderate-to-Severe Rheumatoid Arthritis: A Double-Blind, Randomized, Three-Arm Study.

OBJECTIVES: The aims were to demonstrate pharmacokinetic (PK) similarity between DRL_RI, a proposed rituximab biosimilar, and two reference innovator products (Rituxan® [RTX-US] and MabThera® [RTX-EU]) and compare their pharmacodynamics (PD), efficacy, safety, and immunogenicity in rheumatoid arthritis (RA) patients with inadequate response to methotrexate (MTX)-based therapy and no prior biologic administration. METHODS: In this randomized, double-blind, parallel-group study, 276 patients with moderate-to-severe active RA were randomized to receive DRL_RI, RTX-US, or RTX-EU on days 1 and 15. The primary PK end points included area under the concentration-time curve from time 0 to 336 h after first infusion (AUC0-14 days, first infusion), AUC from day 1 through week 16 (AUC0-∞, entire course), and AUC from time 0 to time of last quantifiable concentration after the second dose (AUC0-t, second infusion). Secondary end points included other PK parameters, such as maximum concentration (Cmax), time to Cmax after each infusion, terminal half-life, systemic clearance, and volume of distribution after the second infusion; PD parameters and efficacy until week 24; safety and immunogenicity at week 24 and 52; and B cell recovery until week 52. AUC from time 0 to time of last quantifiable concentration after the first dose and over the entire course from day 1 through week 16 (AUC0-t, entire course) was analyzed as an exploratory end point. RESULTS: The 91% confidence intervals (CIs) of the geometric mean ratios (GMRs) for the primary end point of AUC0-∞, entire course were within the bioequivalence limits of 80-125% for all comparisons: DRL_RI versus RTX-US 100.37% (92.30-109.14), DRL_RI versus RTX-EU 93.58% (85.98-101.85), and RTX-US versus RTX-EU 93.24% (85.62-101.54). PD outcomes (peripheral blood B-cell depletion and mean change in Disease Activity Score [28 joints]-C-reactive protein), efficacy, safety, and immunogenicity were also comparable between DRL_RI and the reference products. CONCLUSION: DRL_RI, a proposed biosimilar, demonstrated three-way PK similarity with RTX-EU and RTX-US, the reference innovator products, with comparable efficacy, PD, safety, and immunogenicity. CLINICAL TRIALS REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT02296775.

Randomized, Double-Blind, Pharmacokinetic Equivalence Trial Comparing DRL-Rituximab With MabThera in Patients With Diffuse Large B-Cell Lymphoma.

PURPOSE: We sought to compare the pharmacokinetics (PKs) of DRL-rituximab (DRL_RI; potential biosimilar) and innovator rituximab MabThera (Roche, Grenzach-Wyhlen, Germany; reference medicinal product [RMP]) in patients with diffuse large B-cell lymphoma (DLBCL). Efficacy, pharmacodynamics (PDs), safety, and immunogenicity were also compared. PATIENTS AND METHODS: We conducted a double-blind, parallel-group study in patients with untreated DLBCL who were eligible to receive cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) therapy. Patients were randomly assigned at a one-to-one ratio to receive DRL_RI or RMP for six 21-day cycles of rituximab plus CHOP, with 18 months of follow-up after day 1, cycle 6 (C6). Primary end point was C1 PKs, measured as area under the plasma concentration-time curve from day 0 to 21 (AUC0-21 days) and maximum plasma concentration (Cmax). Equivalence was defined as 90% CIs for the DRL_RI/RMP geometric mean ratios (GMRs) within 80% and 125%. Secondary end points included efficacy noninferiority measured by objective response rate (ORR) at C6 and event-free survival and overall survival at 87 weeks, PK equivalence at C6 and PD equivalence (rate of B-cell depletion and repletion), safety, and immunogenicity. The trial was stopped after sufficient patients for primary end point evaluation were enrolled. Secondary end points are reported as observed. RESULTS: A total of 151 patients were randomly assigned (DRL_RI, n = 76; RMP, n = 75). DRL_RI/RMP GMRs for AUC0-21 days and Cmax in C1 were 99.77 (90% CI, 87.60 to 113.63) and 96.19 (90% CI, 88.65 to 104.38), respectively. ORR at C6 for DRL_RI and RMP were 82.0% and 84.8%, respectively. Rates of B-cell depletion/repletion, immunogenicity, and adverse events were comparable in both groups. CONCLUSION: DRL_RI and RMP had equivalent PKs, with comparable efficacy, PDs, safety, and immunogenicity.

Neuroimaging of Emergent and Reemergent Infections.

Infectious diseases emerge and reemerge over the years, and many of them can cause neurologic disease. Several factors contribute to the emergence and reemergence of these conditions, including human population growth, an increase in international travel, the geographic expansion of recognized pathogens to areas where they were previously nonendemic, and greater contact with wild animal reservoirs. The antivaccination social movement has played an important role in the reemergence of infectious diseases, especially some viral conditions. The authors review different viral (arboviruses such as dengue, chikungunya, and Zika virus; enterovirus 71; measles; and influenza), bacterial (syphilis, Lyme disease, and listeriosis), and parasitic (Chagas disease) diseases, focusing primarily on their neurologic complications. Although there are several additional infectious diseases with central nervous system manifestations that could be classified as emergent or reemergent, those listed here are the most relevant from an epidemiologic standpoint and are representative of important public health issues on all continents. The infections caused by these pathogens often show a variety of neuroimaging patterns that can be identified at CT and MRI, and radiology is central to the diagnosis and follow-up of such conditions. Given the increasing relevance of emerging and reemerging infections in clinical practice and public health scenarios, radiologists should be familiar with these infections. Online supplemental material is available for this article. ©RSNA, 2019.