Adjuvant Wilms' tumour 1-specific dendritic cell immunotherapy complementing conventional therapy for paediatric patients with high-grade glioma and diffuse intrinsic pontine glioma: protocol of a monocentric phase I/II clinical trial in Belgium.

INTRODUCTION: Diffuse intrinsic pontine glioma (DIPG) and paediatric high-grade glioma (pHGG) are aggressive glial tumours, for which conventional treatment modalities fall short. Dendritic cell (DC)-based immunotherapy is being investigated as a promising and safe adjuvant therapy. The Wilms' tumour protein (WT1) is a potent target for this type of antigen-specific immunotherapy and is overexpressed in DIPG and pHGG. Based on this, we designed a non-randomised phase I/II trial, assessing the feasibility and safety of WT1 mRNA-loaded DC (WT1/DC) immunotherapy in combination with conventional treatment in pHGG and DIPG. METHODS AND ANALYSIS: 10 paediatric patients with newly diagnosed or pretreated HGG or DIPG were treated according to the trial protocol. The trial protocol consists of leukapheresis of mononuclear cells, the manufacturing of autologous WT1/DC vaccines and the combination of WT1/DC-vaccine immunotherapy with conventional antiglioma treatment. In newly diagnosed patients, this comprises chemoradiation (oral temozolomide 90 mg/m2 daily+radiotherapy 54 Gy in 1.8 Gy fractions) followed by three induction WT1/DC vaccines (8-10×106 cells/vaccine) given on a weekly basis and a chemoimmunotherapy booster phase consisting of six 28-day cycles of oral temozolomide (150-200 mg/m2 on days 1-5) and a WT1/DC vaccine on day 21. In pretreated patients, the induction and booster phase are combined with best possible antiglioma treatment at hand. Primary objectives are to assess the feasibility of the production of mRNA-electroporated WT1/DC vaccines in this patient population and to assess the safety and feasibility of combining conventional antiglioma treatment with the proposed immunotherapy. Secondary objectives are to investigate in vivo immunogenicity of WT1/DC vaccination and to assess disease-specific and general quality of life. ETHICS AND DISSEMINATION: The ethics committee of the Antwerp University Hospital and the University of Antwerp granted ethics approval. Results of the clinical trial will be shared through publication in a peer-reviewed journal and presentations at conferences. TRIAL REGISTRATION NUMBER: NCT04911621.

Case report: Psychosis with catatonia in an adult man: a presentation of neurosarcoidosis.

Introduction: Sarcoidosis is a multisystem non-caseous granulomatous disease of unknown origin with predominant lung involvement and a variable clinical course. Although rare, neuropsychiatric manifestations such as confusion, problems in orientation, memory dysfunction, delusions, hallucinations and catatonia can be presenting features of sarcoidosis with nervous system involvement, also known as neurosarcoidosis. Case description: We present a 39-year-old man with acute-onset vertigo, balance problems and confusion quickly developing delusions, hallucinations, catatonic symptoms and suicidal behaviour. Symptoms appeared to be a manifestation of neurosarcoidosis. Diagnostic assessment: The differential diagnosis of psychosis is broad and should include pertinent auto-immune disorders, paraneoplastic, oncologic, metabolic, and neurodegenerative disorders. Basic systemic screening should include blood and urinary tests, a chest X-ray, brain CT scan and ECG. If neurosarcoidosis is suspected, an MRI of the brain with contrast and lumbar puncture are most appropriate. Multidisciplinary collaboration is essential to arrive at a correct diagnosis and effective management of the patient. Discussion: Despite the large number of sarcoidosis and psychosis studies, the etiology and pathogenesis of both illnesses remain incompletely understood. A common inflammatory etiopathological pathway has been postulated. Conclusions: Clinicians should consider organic causes when confronted with a middle-aged patient experiencing a first psychotic episode with an atypical onset, catatonic features, or dysfunction in orientation and/or memory, a complete lack of a positive familial psychiatric history and/or an atypical response to (psycho)pharmacological treatment.

Anything but Little: a Pictorial Review on Anatomy and Pathology of the Cerebellum.

Despite its small size the cerebellum is an anatomically complex and functionally important part of the brain. Traditionally the cerebellum is viewed as a motor control structure entirely devoted to motor control and learning, but recent functional magnetic resonance imaging (fMRI) studies demonstrated significant involvement of the cerebellum in higher order cognitive functions. The anatomical complexity of the cerebellum is reflected by the several nomenclature systems that exist for the description of cerebellar anatomy. The cerebellum can be affected by a variety of pathological processes, including congenital, infectious and inflammatory, neoplastic, vascular, degenerative and toxic metabolic diseases. The purpose of this pictorial review is to (1) provide a general overview of cerebellar anatomy and function, (2) demonstrate normal cerebellar anatomy on imaging studies, and (3) illustrate both common as well as rare pathological conditions affecting the cerebellum.

Human Herpesvirus-6 Encephalitis.

Teaching point: HHV6 encephalitis is a specific complication to be considered in a patient with neurological symptoms after hematopoietic stem cell transplantation and typically shows symmetrical involvement of the limbic system.

Not Your Everyday FCD: Imaging Findings of Focal Cortical Dysplasia Type 1.

Teaching Point: The imaging findings of focal cortical dysplasia type 1 are less well-known than focal cortical dysplasia type 2 and consist of increased white matter signal intensity and blurring of the gray-white matter in a large region of the brain, with associated segmental or lobar brain atrophy.

The value of four stage vestibular hydrops grading and asymmetric perilymphatic enhancement in the diagnosis of Menière's disease on MRI.

PURPOSE: There is still a clinical-radiologic discrepancy in patients with Menière's disease (MD). Therefore, the purpose of this study was to investigate the reliability of current MRI endolymphatic hydrops (EH) criteria according to Baráth in a larger study population and the clinical utility of new imaging signs such as a supplementary fourth low-grade vestibular EH and the degree of perilymphatic enhancement (PE) in patients with Menière's disease (MD). METHODS: This retrospective study included 148 patients with probable or definite MD according to the 2015 American Academy of Otolaryngology, Head and Neck Surgery criteria who underwent a 4-h delayed intravenous Gd-enhanced 3D-FLAIR MRI between January 2015 and December 2016. Vestibular EH, vestibular PE, cochlear EH, and cochlear PE were reviewed twice by three experienced readers. Cohen's Kappa and multivariate logistic regression were used for analysis. RESULTS: The intra- and inter-reader reliability for the grading of vestibular-cochlear EH and PE was excellent (0.7 < kappa < 0.9). The two most distinctive characteristics to identify MD are cochlear PE and vestibular EH which combined gave a sensitivity and specificity of 79.5 and 93.6%. By addition of a lower grade vestibular EH, the sensitivity improved to 84.6% without losing specificity (92.3%). Cochlear EH nor vestibular PE showed added-value. CONCLUSIONS: MRI using vestibular-cochlear EH and PE grading system is a reliable technique. A four-stage vestibular EH grading system in combination with cochlear PE assessment gives the best diagnostic accuracy to detect MD.

A Typical but Underdiagnosed Nasal Cavity Mass.

Respiratory epithelial adenomatoid hamartoma is a relatively new diagnosis, only added to the World Health Organization classification of tumours in 2005. The lesion results from non-neoplastic overgrowth of glandular tissue in the nasal cavity and rarely in de sinus cavities and is often associated with nasal polyposis. The classical appearance of a bilateral mass in the olfactory cleft causing widening of the olfactory cleft allows the radiologist to suggest the diagnosis on computed tomography or magnetic resonance imaging.

"Unforgettable" - a pictorial essay on anatomy and pathology of the hippocampus.

The hippocampus is a small but complex anatomical structure that plays an important role in spatial and episodic memory. The hippocampus can be affected by a wide range of congenital variants and degenerative, inflammatory, vascular, tumoral and toxic-metabolic pathologies. Magnetic resonance imaging is the preferred imaging technique for evaluating the hippocampus. The main indications requiring tailored imaging sequences of the hippocampus are medically refractory epilepsy and dementia. The purpose of this pictorial review is threefold: (1) to review the normal anatomy of the hippocampus on MRI; (2) to discuss the optimal imaging strategy for the evaluation of the hippocampus; and (3) to present a pictorial overview of the most common anatomic variants and pathologic conditions affecting the hippocampus. TEACHING POINTS: • Knowledge of normal hippocampal anatomy helps recognize anatomic variants and hippocampal pathology. • Refractory epilepsy and dementia are the main indications requiring dedicated hippocampal imaging. • Pathologic conditions centered in and around the hippocampus often have similar imaging features. • Clinical information is often necessary to come to a correct diagnosis or an apt differential.

Quadriscupid Aortic Valve with Concurrent Aortic Stenosis and Insufficiency.

We present the case of a 22-year-old man with a congenital mixed aortic valve dysfunction who underwent cardiac Magnetic Resonance Imaging (MRI) for the assessment of aortic valve morphology and function prior to valve replacement. Cardiac MRI showed a four-leaf-clover aortic valve morphology, the typical presentation of a quadricuspid aortic valve. The patient underwent a successful Bentall procedure to replace the aortic valve, aortic root and ascending aorta. This case report illustrates the MRI findings of a quadricuspid aortic valve with associated aortic stenosis and regurgitation.