Quantification of follicles in human ovarian tissue using image processing software and trained artificial intelligence†.

Cancer survival rates in prepubertal girls and young women have risen in recent decades due to increasingly efficient treatments. However, many such treatments are gonadotoxic, causing premature ovarian insufficiency, loss of fertility, and ovarian endocrine function. Implantation of donor ovarian tissue encapsulated in immune-isolating capsules is a promising method to restore physiological endocrine function without immunosuppression or risk of reintroducing cancer cells harbored by the tissue.

Canadian Consensus Guidelines for the Diagnosis and Treatment of Autoimmune Encephalitis in Adults.

Autoimmune encephalitis is increasingly recognized as a neurologic cause of acute mental status changes with similar prevalence to infectious encephalitis. Despite rising awareness, approaches to diagnosis remain inconsistent and evidence for optimal treatment is limited. The following Canadian guidelines represent a consensus and evidence (where available) based approach to both the diagnosis and treatment of adult patients with autoimmune encephalitis.

MR Susceptibility Separation for Quantifying Lesion Paramagnetic and Diamagnetic Evolution in Relapsing-Remitting Multiple Sclerosis.

Background: Multiple sclerosis (MS) lesion evolution may involve changes in diamagnetic myelin and paramagnetic iron. Conventional quantitative susceptibility mapping (QSM) can provide net susceptibility distribution, but not the discrete paramagnetic and diamagnetic components.

Purpose: To apply susceptibility separation (χ separation) to follow lesion evolution in MS with comparison to R*/R /QSM.

High-resolution diffusion tensor imaging and T2 mapping detect regional changes within the hippocampus in multiple sclerosis.

Hippocampus demyelinating lesions in multiple sclerosis (MS) have been frequently observed in ex vivo histopathological studies; however, they are difficult to image and quantify in vivo. Diffusion tensor imaging (DTI) and T2 mapping could potentially detect such regional in vivo changes if acquired with sufficient spatial resolution. The goal here was to evaluate whether there are focal hippocampal abnormalities in 43 MS patients (35 relapsing-remitting, eight secondary progressive) with and without cognitive impairment (CI) versus 43 controls using high-resolution 1 mm isotropic DTI, as well as complementary methods of T2-weighted and T2 mapping at 3 T.

Inline dual-echo T2 quantification in brain using a fast mapping reconstruction technique.

T2 mapping from 2D proton density and T2-weighted images (PD-T2) using Bloch equation simulations can be time consuming and introduces a latency between image acquisition and T2 map production. A fast T2 mapping reconstruction method is investigated and compared with a previous modeling approach to reduce computation time and allow inline T2 maps on the MRI console. Brain PD-T2 images from five multiple sclerosis patients were used to compare T2 map reconstruction times between the new subtraction method and the Euclidean norm minimization technique.

Elevated ATP via enhanced miRNA-30b, 30c, and 30e downregulates the expression of CD73 in CD8+ T cells of HIV-infected individuals.

CD8+ T cells play a crucial role against chronic viral infections, however, their effector functions are influenced by the expression of co-stimulatory/inhibitory receptors. For example, CD73 works with CD39 to convert highly inflammatory ATP to adenosine. However, its expression on T cells in the context of viral infections has not been well defined.

Diffusion imaging of fornix and interconnected limbic deep grey matter is linked to cognitive impairment in multiple sclerosis.

Diffusion tensor imaging (DTI) and volumetric magnetic resonance imaging (MRI) have shown white matter (WM) and deep grey matter (GM) abnormalities in the limbic system of multiple sclerosis (MS) participants. Structures like the fornix have been associated with cognitive impairment (CI) in MS, but the diffusion metrics are often biased by partial volume effects from cerebrospinal fluid (CSF) due to its small bundle size and intraventricular location. These errors in DTI parameter estimation worsen with atrophy in MS.

Infection of Glia by Human Pegivirus Suppresses Peroxisomal and Antiviral Signaling Pathways.

Human pegivirus (HPgV) infects peripheral leukocytes but was recently shown to be a neurotropic virus associated with leukoencephalitis in humans. In the present study, we investigated the neural cell tropism of HPgV as well as its effects on host immune responses. HPgV wild type (WT) and a mutant virus with a deletion in the HPgV gene (ΔNS2) were able to productively infect human astrocytes and microglia but not neurons or an oligodendrocyte-derived cell line.

Differential disease phenotypes and progression in relapsing-remitting multiple sclerosis: comparative analyses of single Canadian and Saudi Arabian clinics.

Objective: Relapsing-remitting multiple sclerosis (RR-MS) phenotypes differ widely although the variables contributing to this heterogeneity remain uncertain. To assess geographic and ethnic effects on RR-MS phenotypes, we investigated RR-MS patients in Canada and Saudi Arabia.

Methods: A retrospective analysis of patients followed in two MS Clinics was performed in Medina, Saudi Arabia and Edmonton, Canada.

Cross-sectional analysis of peripheral blood mononuclear cells in lymphopenic and non-lymphopenic relapsing-remitting multiple sclerosis patients treated with dimethyl fumarate.

Background: Relapsing-remitting multiple sclerosis (RRMS) is an autoimmune disorder of the central nervous system. Dimethyl Fumarate is a disease-modifying medication used to treat RRMS patients that can induce lymphopenia. We aimed to immunophenotype peripheral blood mononuclear cells (PBMC) in RRMS patients cross-sectionally and examine the characteristics and modifications of lymphopenia over time.

Disability progression in multiple sclerosis is associated with plasma neuroactive steroid profile.

Background: Neuroactive steroids (NASs) exert multiple biological effects on development and inflammation. The effects of NASs on disease progression in multiple sclerosis (MS) are uncertain, prompting analyses of NAS profiles during the transition from clinically isolated syndrome (CIS) to relapsing-remitting (RR) MS.

Methods: Subjects with CIS or RRMS and healthy controls (HCs) were recruited; demographic and clinical data as well as disability scores measured by the Expanded Disability Status Scale (EDSS) were recorded.

Sarcoidosis: a prospective observational cohort from Northern Alberta.

Introduction: Sarcoidosis is a multi-system disease reported to occur with a higher incidence in Alberta than many other health jurisdictions within and outside of Canada. The reasons for this higher incidence are currently not known. Exposure to beryllium can result in a clinically and radiologically identical disease to sarcoidosis.

The Clinical Conundrum of Managing Ischemic Stroke in Patients with Immune Thrombocytopenia.

Guidelines are lacking for management of acute ischemic stroke and stroke prevention in patients with immune thrombocytopenia (ITP). Our aim is to highlight the dilemma inherent in managing patients with both significant bleeding and thrombotic risk factors. In this review, we present two patients with history of ITP who presented with acute ischemic stroke and received tissue plasminogen activator (tPA) and endovascular thrombectomy (EVT), a rare management strategy in this patient population.

Five year iron changes in relapsing-remitting multiple sclerosis deep gray matter compared to healthy controls.

Background: Relapsing-Remitting MS (RRMS) Deep Grey Matter (DGM) 5 year changes were examined using MRI measures of volume, transverse relaxation rate (R2*) and quantitative magnetic susceptibility (QS). By applying Discriminative Analysis of Regional Evolution (DARE), R2* and QS changes from iron and non-iron sources were separated.

Methods: 25 RRMS and 25 age-matched control subjects were studied at baseline and 5-year follow-up.

Human pegivirus-1 associated leukoencephalitis: Clinical and molecular features.

Etiologic diagnosis is uncertain in 35% to 50% of patients with encephalitis, despite its substantial global prevalence and disease burden. We report on 2 adult female patients with fatal leukoencephalitis associated with human pegivirus-1 (HPgV-1) brain infection. Neuroimaging showed inflammatory changes in cerebral white matter.

Discriminative analysis of regional evolution of iron and myelin/calcium in deep gray matter of multiple sclerosis and healthy subjects.

Background: Combined R2* and quantitative susceptibility (QS) has been previously used in cross-sectional multiple sclerosis (MS) studies to distinguish deep gray matter (DGM) iron accumulation and demyelination.

Purpose: We propose and apply discriminative analysis of regional evolution (DARE) to define specific changes in MS and healthy DGM.

Study Type: Longitudinal (baseline and 2-year follow-up) retrospective study.

Characterization of lymphopenia in patients with MS treated with dimethyl fumarate and fingolimod.

Objective: Lymphopenia is a common occurrence of disease-modifying therapies (DMTs) for relapsing-remitting MS (RRMS). The aim of this study was to dissect the prevalence of various lymphocyte subsets in patients with RRMS treated with 2 DMTs commonly associated with lymphopenia, dimethyl fumarate (DMF), and fingolimod (FTY).

Methods: Multicolor flow cytometry and multiplex assays were used to identify up to 50 lymphocyte subpopulations and to examine the expression of multiple cytokines in selected patients.

Trial of Minocycline in a Clinically Isolated Syndrome of Multiple Sclerosis.

Background: On the basis of encouraging preliminary results, we conducted a randomized, controlled trial to determine whether minocycline reduces the risk of conversion from a first demyelinating event (also known as a clinically isolated syndrome) to multiple sclerosis.

Methods: During the period from January 2009 through July 2013, we randomly assigned participants who had had their first demyelinating symptoms within the previous 180 days to receive either 100 mg of minocycline, administered orally twice daily, or placebo. Administration of minocycline or placebo was continued until a diagnosis of multiple sclerosis was established or until 24 months after randomization, whichever came first.

Progressive iron accumulation across multiple sclerosis phenotypes revealed by sparse classification of deep gray matter.

Purpose: To create an automated framework for localized analysis of deep gray matter (DGM) iron accumulation and demyelination using sparse classification by combining quantitative susceptibility (QS) and transverse relaxation rate (R2*) maps, for evaluation of DGM in multiple sclerosis (MS) phenotypes relative to healthy controls.

Materials And Methods: R2*/QS maps were computed using a 4.7T 10-echo gradient echo acquisition from 16 clinically isolated syndrome (CIS), 41 relapsing-remitting (RR), 40 secondary-progressive (SP), 13 primary-progressive (PP) MS patients, and 75 controls.

Cognitive Implications of Deep Gray Matter Iron in Multiple Sclerosis.

Background And Purpose: Deep gray matter iron accumulation is increasingly recognized in association with multiple sclerosis and can be measured in vivo with MR imaging. The cognitive implications of this pathology are not well-understood, especially vis-à-vis deep gray matter atrophy. Our aim was to investigate the relationships between cognition and deep gray matter iron in MS by using 2 MR imaging-based iron-susceptibility measures.

Recovery of accurate T from historical 1.5 tesla proton density and T-weighted images: Application to 7-year T changes in multiple sclerosis brain.

Objective: To determine accurate quantitative transverse relaxation times (T) using retrospective clinical images and apply it to examine 7-year changes in multiple sclerosis (MS) brain.

Methods: A method for T mapping from retrospective proton density (PD) and T-weighted fast spin echo images was recently introduced, but requires measurement of flip angles. We examined whether 1.

Multifocal inflammatory demyelination in a patient with rheumatoid arthritis and treatment complications.

Rheumatoid arthritis (RA) and multiple sclerosis (MS) are both autoimmune diseases that share similar pathogenesis, but the development of MS in RA patients without the treatment of anti-tumor necrosis factor-alpha is rarely reported, which might be attributed to the use of other medications with potential immunosuppressive effects in the treatment of RA. Since MS can be clinically silent and autopsy examination of the central nervous system in RA patients is rarely described, the association of MS with RA may be possibly under-recognized. We report an autopsy case revealing multifocal inflammatory demyelination in a RA patient who had a prolonged use of methotrexate and hydroxychloroquine resulting in hydroxychloroquine-induced myopathies and heart failure.

Medical Tourism for CCSVI Procedures in People with Multiple Sclerosis: An Observational Study.

Background: Many Canadians with multiple sclerosis (MS) have recently travelled internationally to have procedures for a putative condition called chronic cerebrospinal venous insufficiency (CCSVI). Here, we describe where and when they went and describe the baseline characteristics of persons with MS who participated in this non-evidence-based medical tourism for CCSVI procedures.

Methods: We conducted a longitudinal observational study that used online questionnaires to collect patient-reported information about the safety, experiences, and outcomes following procedures for CCSVI.