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.

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.

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.

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.

Neuroinflammation Preceding and Accompanying Primary Central Nervous System Lymphoma: Case Study and Literature Review.

Background: Primary central nervous system lymphoma (PCNSL) is an aggressive lymphoma confined to the CNS. Although the pathogenesis of PCNSL in immunocompetent individuals remains unclear, there have been several case studies demonstrating the "sentinel" inflammatory lesions months before the manifestation of PCNSL. However, the pathologic relationship between the inflammatory lesions and subsequent PCNSL is still unknown.

Rapid Multifocal Neurologic Decline in an Immunocompromised Patient.

A man in his early 70s with a diagnosis of chronic lymphocytic leukemia and being treated with prednisone, fludarabine, cyclophosphamide, and rituximab presented with progressive multifocal neurologic decline. The patient died 2 months after the onset of this decline despite extensive clinical and laboratory investigation and a trial of methylprednisolone therapy. The approach to the immunosuppressed patient with progressive neurologic decline, neuropathologic findings, and final diagnosis are discussed.

Spin echo transverse relaxation and atrophy in multiple sclerosis deep gray matter: A two-year longitudinal study.

Background: Deep gray matter (DGM) is affected in relapsing-remitting multiple sclerosis (RRMS) and may be studied using short-term longitudinal MRI.

Objective: To investigate two-year changes in spin-echo transverse relaxation rate (R2) and atrophy in DGM, and its relationship with disease severity in RRMS patients.

Methods: Twenty six RRMS patients and 26 matched controls were imaged at 4.

Subcortical gray matter segmentation and voxel-based analysis using transverse relaxation and quantitative susceptibility mapping with application to multiple sclerosis.

Purpose: To investigate subcortical gray matter segmentation using transverse relaxation rate (R2 *) and quantitative susceptibility mapping (QSM) and apply it to voxel-based analysis in multiple sclerosis (MS).

Materials And Methods: Voxel-based variation in R2 * and QSM within deep gray matter was examined and compared to standard whole-structure analysis using 37 MS subjects and 37 matched controls. Deep gray matter nuclei (caudate, putamen, globus pallidus, and thalamus) were automatically segmented and morphed onto a custom atlas based on QSM and standard T1 -weighted images.

Decision-making under explicit risk is impaired in multiple sclerosis: relationships with ventricular width and disease disability.

Background: Decision-making is an essential function of everyday life. Decision-making under explicit risk requires developing advantageous decision strategies based on fixed outcomes (e.g.