Differential diagnosis of suspected multiple sclerosis: considerations in people from minority ethnic and racial backgrounds in North America, northern Europe, and Australasia.

The differential diagnosis of suspected multiple sclerosis has been developed using data from North America, northern Europe, and Australasia, with a focus on White populations. People from minority ethnic and racial backgrounds in regions where prevalence of multiple sclerosis is high are more often negatively affected by social determinants of health, compared with White people in these regions. A better understanding of changing demographics, the clinical characteristics of people from minority ethnic or racial backgrounds, and the social challenges they face might facilitate equitable clinical approaches when considering a diagnosis of multiple sclerosis.

Role of B Cells in Relapsing-Remitting and Progressive Multiple Sclerosis and Long-Term Effects of B Cell Depletion.

Depletion of circulating B lymphocytes using anti-CD20 monoclonal antibodies (mAbs) greatly reduces inflammatory activity in relapsing multiple sclerosis (RMS); it reduces progression to a lesser extent in nonrelapsing progressive MS. Mechanisms whereby anti-CD20 mAbs reduce MRI and clinical relapse activity in people with RMS are still being elucidated. Anti-CD20 agents do not fully protect from nonrelapsing disease progression, possibly due to their inability to cross the blood-brain barrier and inability to ameliorate the full extent of biology of MS progression.

Disseminated Aspergillosis in a Patient With Neurosarcoidosis: Persistent Contrast Enhancement in CNS Despite Prolonged Antifungal Treatment: A Case Report.

A 56-year-old Caucasian man was diagnosed with definite neurosarcoidosis after he presented with progressive bilateral lower extremity weakness and dysesthesia. He was started on a combination immunosuppressant regimen of dexamethasone, methotrexate and infliximab. Two months into treatment with immunosuppressants, he developed devastating disseminated aspergillosis which clinically stabilized with aggressive antifungal treatment however had a protracted radiological course despite prolonged anti-fungal treatment for over two years.

Anti-Neurofascin Antibodies Associated with White Matter Diseases of the Central Nervous System: A Red Flag or a Red Herring?

Autoantibodies against nodal and paranodal proteins, specifically anti-neurofascin antibodies (ANFAs), have been recently described in central and peripheral nervous system demyelinating disorders. We retrospectively reviewed the charts of six individuals evaluated at our Multiple Sclerosis Program who tested positive for serum ANFAs on Western blot. We describe these patients' clinical and diagnostic findings and attempt to identify features that might guide clinicians in checking for ANFAs.

Clinical trials in multiple sclerosis: past, present, and future.

For the past four decades, multiple sclerosis (MS) has been a focus for clinical trial development and execution. Advances in translational neuroimmunology have led to the development of effective disease-modifying therapies (DMTs) that greatly benefit patients with MS and mitigate their burden of disease. These achievements also stem from continued progress made in the definition and discovery of sensitive disease diagnostic criteria, objective disability assessment scales, precise imaging techniques, and disease-specific biomarkers.

Aging and efficacy of disease-modifying therapies in multiple sclerosis: a meta-analysis of clinical trials.

Background: Disease-modifying therapies (DMTs) for multiple sclerosis (MS) are approved for the treatment of disease activity and are effective in reducing relapses and new magnetic resonance imaging (MRI) lesions. However, disease activity generally subsides with time, and age-dependent changes in DMT efficacy are not well-established. We aimed to investigate whether age impacts the efficacy of DMTs in treating disease activity in patients with relapsing-remitting MS (RRMS).

Adverse event profile differences between rituximab and ocrelizumab: Findings from the FDA Adverse Event Reporting Database.

Background: Rituximab and ocrelizumab are anti-CD20 monoclonal antibodies that have shown a marked reduction in multiple sclerosis (MS) inflammatory activity. However, their real-world safety profile has not been adequately compared.

Objective: To investigate the adverse event (AE) profile of rituximab and ocrelizumab reported to the Food and Drug Administration Adverse Event Reporting System (FAERS) database.

Diffusion basis spectrum imaging for identifying pathologies in MS subtypes.

Diffusion basis spectrum imaging (DBSI) combines discrete anisotropic diffusion tensors and the spectrum of isotropic diffusion tensors to model the underlying multiple sclerosis (MS) pathologies. We used clinical MS subtypes as a surrogate of underlying pathologies to assess DBSI as a biomarker of pathology in 55 individuals with MS. Restricted isotropic fraction (reflecting cellularity) and fiber fraction (representing apparent axonal density) were the most important DBSI metrics to classify MS using brain white matter lesions.

The association between handedness and clinicodemographic characteristics in people with multiple sclerosis: a brief report.

A relationship between handedness and clinicodemographic profiles of people with multiple sclerosis was sought using data from the Multiple Sclerosis Partners Advancing Technology Health Solutions network of 10 multiple sclerosis centers in the USA and Europe. Handedness data were available for 8888 multiple sclerosis patients, of which 917 (10.3%) were left-handed.

Histopathological correlation of diffusion basis spectrum imaging metrics of a biopsy-proven inflammatory demyelinating brain lesion: A brief report.

Diffusion basis spectrum imaging (DBSI) models diffusion-weighted magnetic resonance imaging (MRI) signals as a combination of discrete anisotropic diffusion tensors and a spectrum of isotropic diffusion tensors. Here, we report the histopathological correlates of DBSI in the biopsied brain tissue of a patient with an inflammatory demyelinating lesion typical of multiple sclerosis (MS). Increased radial diffusivity (marker of demyelination), decreased fiber fraction (apparent axonal density), elevated nonrestricted isotropic fraction (marker of vasogenic edema), but unchanged axial diffusivity (marker of integrity of residual axons) seen in the lesion appeared consistent with histopathological findings of inflammatory demyelination with relative axonal sparing.

A case of oligodendroglioma and multiple sclerosis: Occam's razor or Hickam's dictum?

Tumefactive appearing lesions on brain imaging can cause a diagnostic dilemma. We report a middle-aged man who presented with right-sided optic neuritis. A brain MRI showed enhancement of the right optic nerve, and non-enhancing white matter lesions including a 3 cm right frontal lesion with adjacent gyral expansion.

Natalizumab: Perspectives from the Bench to Bedside.

Probably no other disease-modifying drug for multiple sclerosis has a more fascinating story than natalizumab from both the bench to bedside perspective and the postmarketing experience standpoint. Natalizumab is a monoclonal antibody that inhibits the trafficking of lymphocytes from the blood into the central nervous system by blocking the adhesion molecule α4-integrin. Natalizumab was approved as a disease-modifying drug for relapsing remitting multiple sclerosis only 12 years after the discovery of its target molecule-a time line that is rather fast for drug development.

Evaluating the safety of β-interferons in MS: A series of nested case-control studies.

Objective: To examine the association between interferon-β (IFN-β) and potential adverse events using population-based health administrative data in British Columbia, Canada.

Methods: Patients with relapsing-remitting multiple sclerosis (RRMS) who were registered at a British Columbia Multiple Sclerosis Clinic (1995-2004) were eligible for inclusion and were followed up until death, absence from British Columbia, exposure to a non-IFN-β disease-modifying drug, or December 31, 2008. Incidence rates were estimated for each potential adverse event (selected a priori and defined with ICD-9/10 diagnosis codes from physician and hospital claims).

Finger tapping impairments are highly sensitive for evaluating upper motor neuron lesions.

Background: Identifying highly sensitive and reliable neurological exam components are crucial in recognizing clinical deficiencies. This study aimed to investigate finger tapping performance differences between patients with CNS demyelinating lesions and healthy control subjects.

Methods: Twenty-three patients with multiple sclerosis or clinically isolated syndrome with infratentorial and/or cervical cord lesions on MRI, and 12 healthy controls were videotaped while tapping the tip of the index finger against the tip and distal crease of the thumb using both the dominant and non-dominant hand.

Natalizumab for Multiple Sclerosis: A Case in Point for the Impact of Translational Neuroimmunology.

Advances in translational neuroimmunology over the last two decades have revolutionized the treatment of relapsing forms of multiple sclerosis. A pathological hallmark of multiple sclerosis is the presence of leukocytes in the areas of disease activity in the CNS. Natalizumab inhibits the trafficking of lymphocytes from the blood into the brain and spinal cord by blocking the adhesion molecule α-integrin.

Disability progression in aggressive multiple sclerosis.

Objective: To examine disease progression in 'aggressive' multiple sclerosis (MS), British Columbia, Canada (1980-2009).

Methods: Aggressive (or 'malignant') MS was defined as Expanded Disability Status Scale (EDSS) ⩾6 within 5 years from onset. The first EDSS ⩾6 was termed 'baseline'.

Effectiveness of intratracheal salbutamol in addition to surfactant on the clinical course of newborns with respiratory distress syndrome: a clinical trial.

Background: In addition to surfactant deficiency, increase of lung fluid content and secretion of fluid derived from the blood participate in the pathogenesis of RDS in newborns. We hypothesized that the administration of salbutamol (β-agonist) to increase lung fluid absorption would decrease the INSURE failure rate in newborns with respiratory distress syndrome (RDS) treated with intratracheal surfactant.

Methods: Design Blinded, randomized clinical trial study.

Therapeutic Advances and Future Prospects in Progressive Forms of Multiple Sclerosis.

Identifying effective therapies for the treatment of progressive forms of multiple sclerosis (MS) is a highly relevant priority and one of the greatest challenges for the global MS community. Better understanding of the mechanisms involved in progression of the disease, novel trial designs, drug repurposing strategies, and new models of collaboration may assist in identifying effective therapies. In this review, we discuss various therapies under study in phase II or III trials, including antioxidants (idebenone); tyrosine kinase inhibitors (masitinib); sphingosine receptor modulators (siponimod); monoclonal antibodies (anti-leucine-rich repeat and immunoglobulin-like domain containing neurite outgrowth inhibitor receptor-interacting protein-1, natalizumab, ocrelizumab, intrathecal rituximab); hematopoetic stem cell therapy; statins and other possible neuroprotective agents (amiloride, riluzole, fluoxetine, oxcarbazepine); lithium; phosphodiesterase inhibitors (ibudilast); hormone-based therapies (adrenocorticotrophic hormone and erythropoietin); T-cell receptor peptide vaccine (NeuroVax); autologous T-cell immunotherapy (Tcelna); MIS416 (a microparticulate immune response modifier); dopamine antagonists (domperidone); and nutritional supplements, including lipoic acid, biotin, and sunphenon epigallocatechin-3-gallate (green tea extract).