Ocrelizumab associates with reduced cerebrospinal fluid B and CD20 CD4 T cells in primary progressive multiple sclerosis.

The anti-CD20 monoclonal antibody ocrelizumab reduces disability progression in primary progressive multiple sclerosis. CD20 is a prototypical B-cell marker; however, subpopulations of CD4 and CD8 T cells in peripheral blood and cerebrospinal fluid also express low levels of CD20 (CD20). Therefore, direct targeting and depletion of these CD20 T-cell subpopulations may contribute to the therapeutic effect of ocrelizumab.

Disease activity in primary progressive multiple sclerosis: a systematic review and meta-analysis.

Background: Disease activity in multiple sclerosis (MS) is defined as presence of relapses, gadolinium enhancing lesions and/or new or enlarging lesions on MRI. It is associated with efficacy of immunomodulating therapies (IMTs) in primary progressive MS (PPMS). However, a thorough review on disease activity in PPMS is lacking.

Real-world challenges in the diagnosis of primary progressive multiple sclerosis.

Background And Purpose: Despite the 2017 revisions to the McDonald criteria, diagnosing primary progressive multiple sclerosis (PPMS) remains challenging. To improve clinical practice, the aim was to identify frequent diagnostic challenges in a real-world setting and associate these with the performance of the 2010 and 2017 PPMS diagnostic McDonald criteria.

Methods: Clinical, radiological and laboratory characteristics at the time of diagnosis were retrospectively recorded from designated PPMS patient files.

Human T-bet+ B cell development is associated with BTK activity and suppressed by evobrutinib.

Recent clinical trials have shown promising results for the next-generation Bruton's tyrosine kinase (BTK) inhibitor evobrutinib in the treatment of multiple sclerosis (MS). BTK has a central role in signaling pathways that govern the development of B cells. Whether and how BTK activity shapes B cells as key drivers of MS is currently unclear.

Distinct Effector Programs of Brain-Homing CD8 T Cells in Multiple Sclerosis.

The effector programs of CD8 memory T cells are influenced by the transcription factors RUNX3, EOMES and T-bet. How these factors define brain-homing CD8 memory T cells in multiple sclerosis (MS) remains unknown. To address this, we analyzed blood, CSF and brain tissues from MS patients for the impact of differential RUNX3, EOMES and T-bet expression on CD8 T cell effector phenotypes.

Brain-homing CD4 T cells display glucocorticoid-resistant features in MS.

Objective: To study whether glucocorticoid (GC) resistance delineates disease-relevant T helper (Th) subsets that home to the CNS of patients with early MS.

Methods: The expression of key determinants of GC sensitivity, multidrug resistance protein 1 (MDR1/) and glucocorticoid receptor (GR/), was investigated in proinflammatory Th subsets and compared between natalizumab-treated patients with MS and healthy individuals. Blood, CSF, and brain compartments from patients with MS were assessed for the recruitment of GC-resistant Th subsets using fluorescence-activated cell sorting (FACS), quantitative polymerase chain reaction (qPCR), immunohistochemistry, and immunofluorescence.

CT within 6 hours of headache onset to rule out subarachnoid hemorrhage in nonacademic hospitals.

Objective: To investigate whether staff radiologists working in nonacademic hospitals can adequately rule out subarachnoid hemorrhage (SAH) on head CT <6 hours after headache onset.

Methods: In a multicenter, retrospective study, we studied a consecutive series of patients presenting with acute headache to 11 nonacademic hospitals. Inclusion criteria were (1) normal level of consciousness without focal deficits, (2) head CT <6 hours after headache onset and reported negative for the presence of SAH by a staff radiologist, and (3) subsequent CSF spectrophotometry.