Advances in assessment and cognitive neurorehabilitation of HIV-related neurocognitive impairment.

Neurocognitive impairment (NCI) is present in around 40% of people with HIV and substantially affects everyday life, adherence to combined antiretroviral therapy (cART) and overall life expectancy. Suboptimal therapy regimen, opportunistic infections, substance abuse and highly prevalent psychiatric co-morbidities contribute to NCI in people with HIV. In this review, we highlight the need for efficacious treatment of HIV-related NCI through pharmacological approaches and cognitive neurorehabilitation, discussing recent randomized controlled trials in this domain.

EBNA-1 and VCA-p18 immunoglobulin markers link Epstein-Barr virus immune response and brain's myelin content to fatigue in a community-dwelling cohort.

Given the association of Epstein-Barr virus (EBV) with subjective perception of fatigue and demyelination in clinical conditions, the question about potential subclinical effects in the adult general population remains open. We investigate the association between individuals' EBV immune response and perceived fatigue in a community dwelling cohort (n = 864, age 62 ± 10 years old; 49% women) while monitoring brain tissue properties. Fatigue levels are assessed with the established fatigue severity scale, the EBNA-1 and VCA p18 immunoglobulin G (IgG) chronic response - with multiplex serology and the estimates of local brain volume, myelin content, and axonal density - using relaxometry- and multi-shell diffusion-based magnetic resonance imaging (MRI).

Serum Glial Fibrillary Acidic Protein and Neurofilament Light Chain Levels Reflect Different Mechanisms of Disease Progression under B-Cell Depleting Treatment in Multiple Sclerosis.

Objective: To investigate the longitudinal dynamics of serum glial fibrillary acidic protein (sGFAP) and serum neurofilament light chain (sNfL) levels in people with multiple sclerosis (pwMS) under B-cell depleting therapy (BCDT) and their capacity to prognosticate future progression independent of relapse activity (PIRA) events.

Methods: A total of 362 pwMS (1,480 samples) starting BCDT in the Swiss Multiple Sclerosis (MS) Cohort were included. sGFAP levels in 2,861 control persons (4,943 samples) provided normative data to calculate adjusted Z scores.

Clinical relevance of paramagnetic rim lesion heterogeneity in multiple sclerosis.

Objective: Previous studies reveal heterogeneity in terms of paramagnetic rim lesions (PRL) associated tissue damage. We investigated the physiopathology and clinical implications of this heterogeneity.

Methods: In 103 MS patients (72 relapsing and 31 progressive), brain lesions were manually segmented on 3T 3D-FLAIR and rim visibility was assessed with a visual confidence level score (VCLS) on 3D-EPI phase.

Contrast-Enhancing Lesion Segmentation in Multiple Sclerosis: A Deep Learning Approach Validated in a Multicentric Cohort.

The detection of contrast-enhancing lesions (CELs) is fundamental for the diagnosis and monitoring of patients with multiple sclerosis (MS). This task is time-consuming and suffers from high intra- and inter-rater variability in clinical practice. However, only a few studies proposed automatic approaches for CEL detection.

Presentation and Outcome in S1P-RM and Natalizumab-Associated Progressive Multifocal Leukoencephalopathy: A Multicenter Cohort Study.

Background And Objectives: Progressive multifocal leukoencephalopathy (PML) is a severe neurologic disease resulting from JC virus reactivation in immunocompromised patients. Certain multiple sclerosis (MS) disease-modifying therapies (DMTs) are associated with PML risk, such as natalizumab and, more rarely, sphingosine-1-phosphate receptor modulators (S1P-RMs). Although natalizumab-associated PML is well documented, information on S1P-RM-associated PML is limited.

Exploring the role of brain-derived extracellular vesicles in viral infections: from pathological insights to biomarker potential.

Extracellular vesicles (EVs) are membrane-bound vesicles secreted by all cell types that play a central role in cell-to-cell communication. Since these vesicles serve as vehicles of cellular content (nucleic acids, proteins and lipids) with the potential to cross biological barriers, they represent a novel attractive window into an otherwise inaccessible organ, such as the brain. The composition of EVs is cell-type specific and mirrors the physiological condition of the cell-of-origin.

Enlarged perivascular spaces are associated with brain microangiopathy and aging in multiple sclerosis.

Background: Growing evidence links brain-MRI enlarged perivascular spaces (EPVS) and multiple sclerosis (MS), but their role remains unclear.

Objective: This study aimed to investigate the cross-sectional associations of EPVS with several neuroinflammatory and neurodegenerative features in a large multicentric-MS cohort.

Methods: In total, 207 patients underwent 3T axial-T2-weighted brain-MRI for EPVS assessment (EPVS dichotomized into high/low according to ⩾ 2/< 2 rating categories).

Central Vein Sign, Cortical Lesions, and Paramagnetic Rim Lesions for the Diagnostic and Prognostic Workup of Multiple Sclerosis.

Background And Objectives: The diagnosis of multiple sclerosis (MS) can be challenging in clinical practice because MS presentation can be atypical and mimicked by other diseases. We evaluated the diagnostic performance, alone or in combination, of the central vein sign (CVS), paramagnetic rim lesion (PRL), and cortical lesion (CL), as well as their association with clinical outcomes.

Methods: In this multicenter observational study, we first conducted a cross-sectional analysis of the CVS (proportion of CVS-positive lesions or simplified determination of CVS in 3/6 lesions-Select3*/Select6*), PRL, and CL in MS and non-MS cases on 3T-MRI brain images, including 3D T2-FLAIR, T2*-echo-planar imaging magnitude and phase, double inversion recovery, and magnetization prepared rapid gradient echo image sequences.

Herpes simplex encephalitis due to a mutation in an E3 ubiquitin ligase.

Encephalitis is a rare and potentially fatal manifestation of herpes simplex type 1 infection. Following genome-wide genetic analyses, we identified a previously uncharacterized and very rare heterozygous variant in the E3 ubiquitin ligase WWP2, in a 14-month-old girl with herpes simplex encephalitis. The p.

[Discontinuing disease-modifying therapies in multiple sclerosis].

Aging in multiple sclerosis (MS) leads to altered clinical manifestations, where the pathophysiology shifts towards compartmentalized inflammation that drives clinical progression independent of relapse activity. Consequently, the effectiveness of disease-modifying therapies (DMTs) diminishes in older patients, coinciding with an elevated risk of adverse events. This raises the question of whether MS therapies should be discontinued after a certain age, which is often proposed for patients over 55 years.

[Treatments for multiple sclerosis: update].

The management of multiple sclerosis (MS) has undergone a veritable revolution in recent years, with the arrival of highly effective treatments. In some cases, therapeutic discussions even precede the first clinical signs of the disease. The aim of this review is to present the therapeutic arsenal of progression-preventing treatments available in 2024 for MS, with anti-CD20 antibodies taking pride of place, also available for certain progressive forms of MS.

[Management of chronic inflammatory demyelinating polyradiculoneuropathy].

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is the most common chronic autoimmune neuropathy. Its management has considerably evolved over the last decade. In 2021, the diagnostic guidelines for CIDP were updated and the diagnostic criteria simplified.

[The diagnostic challenge of autoimmune encephalitis].

Autoimmune encephalitis encompasses a spectrum of neurological disorders characterized by an autoimmune response directed against neurons and glia. Around two-thirds of cases exhibit autoantibodies targeting neuronal or glial antigens in the cerebrospinal fluid and/or serum. The diagnosis is based on specific criteria combining a subacute clinical presentation and complementary test results.

Association of Spinal Cord Atrophy and Brain Paramagnetic Rim Lesions With Progression Independent of Relapse Activity in People With MS.

Background And Objectives: Progression independent of relapse activity (PIRA) is a crucial determinant of overall disability accumulation in multiple sclerosis (MS). Accelerated brain atrophy has been shown in patients experiencing PIRA. In this study, we assessed the relation between PIRA and neurodegenerative processes reflected by (1) longitudinal spinal cord atrophy and (2) brain paramagnetic rim lesions (PRLs).

Neurofilament Light Chain Elevation and Disability Progression in Multiple Sclerosis.

Importance: Mechanisms contributing to disability accumulation in multiple sclerosis (MS) are poorly understood. Blood neurofilament light chain (NfL) level, a marker of neuroaxonal injury, correlates robustly with disease activity in people with MS (MS); however, data on the association between NfL level and disability accumulation have been conflicting.

Objective: To determine whether and when NfL levels are elevated in the context of confirmed disability worsening (CDW).

SARS-CoV-2 infects epithelial cells of the blood-cerebrospinal fluid barrier rather than endothelial cells or pericytes of the blood-brain barrier.

Background: As a consequence of SARS-CoV-2 infection various neurocognitive and neuropsychiatric symptoms can appear, which may persist for several months post infection. However, cell type-specific routes of brain infection and underlying mechanisms resulting in neuroglial dysfunction are not well understood.

Methods: Here, we investigated the susceptibility of cells constituting the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) of the choroid plexus (ChP) to SARS-CoV-2 infection using human induced pluripotent stem cell (hiPSC)-derived cellular models and a ChP papilloma-derived epithelial cell line as well as ChP tissue from COVID-19 patients, respectively.

Comprehensive proteomic analysis of JC polyomavirus-infected human astrocytes and their extracellular vesicles.

Progressive multifocal leukoencephalopathy is a crimpling demyelinating disease of the central nervous system caused by JC polyomavirus (JCPyV). Much about JCPyV propagation in the brain remains obscure because of a lack of proper animal models to study the virus in the context of the disease, thus hampering efforts toward the development of new antiviral strategies. Here, having established a robust and representative model of JCPyV infection in human-induced pluripotent stem cell-derived astrocytes, we are able to fully characterize the effect of JCPyV on the biology of the cells and show that the proteomic signature observed for JCPyV-infected astrocytes is extended to extracellular vesicles (EVs).

Bridging the Gap: Immunotherapy in Progressive Multifocal Leukoencephalopathy: A New Hope?

Progressive multifocal leukoencephalopathy (PML) is a severe infection of the CNS occurring in immunocompromised individuals in which large demyelinating lesions are induced by polyomavirus JC (JCV). In the absence of effective antiviral treatment, control of the infection relies on restoring anti-JCV immunity. Thus, particularly in long-standing immunocompromising conditions such as organ transplantation, lymphoproliferative disorders, or idiopathic lymphopenia, new strategies to boost anti-JCV immune responses are needed.