Multiple Sclerosis Therapy Consensus Group (MSTCG): position statement on disease-modifying therapies for multiple sclerosis (white paper).

Multiple sclerosis is a complex, autoimmune-mediated disease of the central nervous system characterized by inflammatory demyelination and axonal/neuronal damage. The approval of various disease-modifying therapies and our increased understanding of disease mechanisms and evolution in recent years have significantly changed the prognosis and course of the disease. This update of the Multiple Sclerosis Therapy Consensus Group treatment recommendation focuses on the most important recommendations for disease-modifying therapies of multiple sclerosis in 2021. Our recommendations are based on current scientific evidence and apply to those medications approved in wide parts of Europe, particularly German-speaking countries (Germany, Austria, and Switzerland).

[Multiple sclerosis treatment consensus group (MSTCG): position paper on disease-modifying treatment of multiple sclerosis 2021 (white paper)]. / Multiple Sklerose Therapie Konsensus Gruppe (MSTKG): Positionspapier zur verlaufsmodifizierenden Therapie der Multiplen Sklerose 2021 (White Paper).

Multiple sclerosis is a complex, autoimmune-mediated disease of the central nervous system characterized by inflammatory demyelination and axonal/neuronal damage. The approval of various disease-modifying therapies and our increased understanding of disease mechanisms and evolution in recent years have significantly changed the prognosis and course of the disease. This update of the Multiple Sclerosis Therapy Consensus Group treatment recommendation focuses on the most important recommendations for disease-modifying therapies of multiple sclerosis in 2021. Our recommendations are based on current scientific evidence and apply to those medications approved in wide parts of Europe, particularly German-speaking countries (Germany, Austria, Switzerland).

Delayed onset hypophysitis after therapy with daclizumab for multiple sclerosis - A report of two cases.

Daclizumab (DAC), a humanized monoclonal antibody that binds to the interleukin (IL)-2-receptor alpha chain, was approved in May 2016 for treatment of relapsing-remitting multiple sclerosis (RRMS). Approval was suspended in March 2018 after occurrence of severe liver failure and fatal meningoencephalitis in several patients treated with DAC. We report the clinical, laboratory and neuroimaging findings of 2 patients, who developed hypophysitis about 4 months after cessation of therapy with DAC. This report identifies delayed onset hypophysitis as a previously unrecognized severe side effect of DAC, highlighting the importance of continuous pharmacovigilance and patient monitoring even after cessation of DAC therapy.

A marker-free registration method for standing X-ray panorama reconstruction for hip-knee-ankle axis deformity assessment.

Accurate measurement of knee alignment, quantified by the hip-knee-ankle (HKA) angle (varus-valgus), serves as an essential biomarker in the diagnosis of various orthopaedic conditions and selection of appropriate therapies. Such angular deformities are assessed from standing X-ray panoramas. However, the limited field-of-view of traditional X-ray imaging systems necessitates the acquisition of several sector images to capture an individual's standing posture, and their subsequent 'stitching' to reconstruct a panoramic image. Such panoramas are typically constructed manually by an X-ray imaging technician, often using various external markers attached to the individual's clothing and visible in two adjacent sector images. To eliminate human error, user-induced variability, improve consistency and reproducibility, and reduce the time associated with the traditional manual 'stitching' protocol, here we propose an automatic panorama construction method that only relies on anatomical features reliably detected in the images, eliminating the need for any external markers or manual input from the technician. The method first performs a rough segmentation of the femur and the tibia, then the sector images are registered by evaluating a distance metric between the corresponding bones along their medial edge. The identified translations are then used to generate the standing panorama image. The method was evaluated on 95 patient image datasets from a database of X-ray images acquired across 10 clinical sites as part of the screening process for a multi-site clinical trial. The panorama reconstruction parameters yielded by the proposed method were compared to those used for the manual panorama construction, which served as gold-standard. The horizontal translation differences were 0:43 ± 1:95 mm 0:26 ± 1:43 mm for the femur and tibia respectively, while the vertical translation differences were 3:76 ± 22:35 mm and 1:85 ± 6:79 mm for the femur and tibia, respectively. Our results showed no statistically significant differences between the HKA angles measured using the automated vs. the manually generated panoramas, and also led to similar decisions with regards to the patient inclusion/exclusion in the clinical trial. Thus, the proposed method was shown to provide comparable performance to manual panorama construction, with increased efficiency, consistency and robustness.

Alemtuzumab in the treatment of multiple sclerosis: patient selection and special considerations.

Multiple sclerosis (MS) is among the most common chronic inflammatory diseases of the central nervous system. Although not curable, the constantly increasing armamentarium of disease-modifying drugs now allows control of disease activity in many patients. The humanized monoclonal antibody alemtuzumab is a powerful drug licensed for the treatment of MS. Upon binding to the CD52 surface protein on CD4+ and CD8+ T cells, B cells, and monocytes, circulating CD52+ cells are eliminated via antibody- and complement-mediated lysis, and a less autoreactive adaptive immune system is reconstituted. The efficacy of alemtuzumab in terms of both clinical and magnetic resonance imaging outcomes has been demonstrated in several phase II/III trials including long-term extensions and follow-up studies. Treatment response to alemtuzumab is strongest as long as active inflammation is the predominant pathophysiological feature, and it is becoming less efficacious in neurodegeneration-dominated later stages of the disease. Thus, the optimal placement of alemtuzumab within treatment algorithms of MS is crucial. The impressive efficacy of alemtuzumab is counteracted by a less favorable safety profile. Besides usually manageable infusion-associated side effects, development of secondary autoimmunity in almost half of treated patients is the most disconcerting risk of alemtuzumab. The high frequency, the delayed occurrence, and the potentially severe course of secondary autoimmune diseases require awareness and a close long-term monitoring of patients treated with alemtuzumab. Biomarkers that would allow prediction of treatment response to alemtuzumab on the one hand and identification of patients at risk for the development of secondary autoimmune diseases on the other are not yet available. Thus, the overall success of alemtuzumab treatment critically depends on the patient selection. The aim of this article is therefore, to characterize the significance of alemtuzumab in the treatment of MS with a focus on the selection of the optimal patient.

Hepatitis E masquerading as drug-induced liver injury.

The patient presented below gives us the opportunity to discuss challenges in the diagnosis of drug-induced liver injury in an era of increasing awareness of hepatitis E.

Fusion viewer: a new tool for fusion and visualization of multimodal medical data sets.

A new application, Fusion Viewer, available for free, has been designed and implemented with a modular object-oriented design. The viewer provides both traditional and novel tools to fuse 3D data sets such as CT (computed tomography), MRI (magnetic resonance imaging), PET (positron emission tomography), and SPECT (single photon emission tomography) of the same subject, to create maximum intensity projections (MIP) and to adjust dynamic range. In many situations, it is desirable and advantageous to acquire biomedical images in more than one modality. For example, PET can be used to acquire functional data, whereas MRI can be used to acquire morphological data. In some situations, a side-by-side comparison of the images provides enough information, but in most of the cases it may be necessary to have the exact spatial relationship between the modalities presented to the observer. To accomplish this task, the images need to first be registered and then combined (fused) to create a single image. In this paper, we discuss the options for performing such fusion in the context of multimodal breast imaging. Additionally, a novel spline-based dynamic range technique is presented in detail. It has the advantage of obtaining a high level of contrast in the intensity range of interest without discarding the intensity information outside of this range while maintaining a user interface similar to the standard window/level windowing procedure.

Execution of the SimSET Monte Carlo PET/SPECT simulator in the condor distributed computing environment.

SimSET is a package for simulation of emission tomography data sets. Condor is a popular distributed computing environment. Simple C/C++ applications and shell scripts are presented which allow the execution of SimSET on the Condor environment. This is accomplished without any modification to SimSET by executing multiple instances and using its combinebin utility. This enables research facilities without dedicated parallel computing systems to utilize the idle cycles of desktop workstations to greatly reduce the run times of their SimSET simulations. The necessary steps to implement this approach in other environments are presented along with sample results.

MRI/PET nonrigid breast-image registration using skin fiducial markers.

We propose a finite-element method (FEM) deformable breast model that does not require elastic breast data for nonrigid PET/MRI breast image registration. The model is applicable only if the stress conditions in the imaged breast are virtually the same in PET and MRI. Under these conditions, the observed intermodality displacements are solely due the imaging/reconstruction process. Similar stress conditions are assured by use of an MRI breast-antenna replica for breast support during PET, and use of the same positioning. The tetrahedral volume and triangular surface elements are used to construct the FEM mesh from the MRI image. Our model requires a number of fiducial skin markers (FSM) visible in PET and MRI. The displacement vectors of FSMs are measured followed by the dense displacement field estimation by first distributing the displacement, vectors linearly over the breast surface and then distributing them throughout the volume. Finally, the floating MRI image is warped to a fixed PET image, by using an appropriate shape function in the interpolation from mesh nodes to voxels. We tested our model on an elastic breast phantom with simulated internal lesions and on a small number of patients imaged, with FMS using PET and MRI. Using simulated lesions (in phantom) and real lesions (in patients) visible in both PET and MRI, we established that the target registration error (TRE) is below two pet voxels.