Differential Protein Expression in Extracellular Vesicles Defines Treatment Responders and Non-Responders in Multiple Sclerosis.

Multiple sclerosis (MS) remains the leading cause of neurological disability among young adults worldwide, underscoring the urgent need to define the best therapeutic strategy. Recent advances in proteomics have deepened our understanding of treatment mechanisms and revealed promising biomarkers for predicting therapeutic outcomes. This study focuses on the identification of a protein profile of circulating extracellular vesicles (EVs) derived from neurons, oligodendrocytes, and B and T cells able to differentiate treatment responders and non-responders in 80 patients with MS.

Antibody Content against Epstein-Barr Virus in Blood Extracellular Vesicles Correlates with Disease Activity and Brain Volume in Patients with Relapsing-Remitting Multiple Sclerosis.

We aimed to analyze whether EVs carry antibodies against EBV antigens and the possibility that they could serve as diagnostic and disease activity blood biomarkers in RRMS. This was a prospective and observational study including patients with RRMS with active and inactive disease and healthy controls. Blood EVs were isolated by precipitation.

Dual role of peripheral B cells in multiple sclerosis: emerging remote players in demyelination and novel diagnostic biomarkers.

Introduction: Multiple sclerosis is an inflammatory and demyelinating disease caused by a pathogenic immune response against the myelin sheath surfaces of oligodendrocytes. The demyelination has been classically associated with pathogenic B cells residing in the central nervous system that release autoreactive antibodies against myelin. The aim of the present study was to investigate whether extracellular vesicles (EVs) mediate delivery of myelin autoreactive antibodies from peripheral B cells against oligodendrocytes in multiple sclerosis (MS) and to analyze whether these EVs could mediate demyelination .

Brain and immune system-derived extracellular vesicles mediate regulation of complement system, extracellular matrix remodeling, brain repair and antigen tolerance in Multiple sclerosis.

Background: Multiple sclerosis (MS) is an immune-mediated central nervous system disease whose course is unpredictable. Finding biomarkers that help to better comprehend the disease's pathogenesis is crucial for supporting clinical decision-making. Blood extracellular vesicles (EVs) are membrane-bound particles secreted by all cell types that contain information on the disease's pathological processes.

Therapeutic plasma exchange for myasthenia gravis, Guillain-Barre syndrome, and other immune-mediated neurological diseases, over a 40-year experience.

Background: Therapeutic plasma exchange (TPE) was first used in neurology in the 1980s for myasthenia gravis (MG) and Guillain-Barré syndrome (GBS). Indications have since grown. Fear of complications with this treatment modality limit its use.

Clinical manifestations of the anti-IgLON5 disease.

Objective: To report the presentation, main syndromes, human leukocyte antigen (HLA) association, and immunoglobulin G (IgG) subclass in the anti-IgLON5 disease: a disorder with parasomnias, sleep apnea, and IgLON5 antibodies.

Methods: This was a retrospective clinical analysis of 22 patients. The IgG subclass was determined using reported techniques.

Differential glatiramer acetate treatment persistence in treatment-naive patients compared to patients previously treated with interferon.

Background: In the treatment of multiple sclerosis, a change of therapy is considered after treatment failure or adverse events. Although disease modifying drugs' (DMD) efficacy and side effects have been fully analysed in clinical trials, the effects of previous therapy use are less well studied. We aimed to study medication persistence with glatiramer acetate in treatment-naive patients and in patients previously treated with interferon.

Gamma-aminobutyric acid GABRA4, GABRE, and GABRQ receptor polymorphisms and risk for essential tremor.

Some clinical and experimental data suggest a possible role of γ-aminobutyrate (GABA)-ergic mechanisms in the pathophysiology of essential tremor (ET). We studied the allelic and genotype frequencies of the single nucleotide polymorphisms, such as GABRA4-L26M (Leu26Met, rs2229940), GABRE-S102A (Ser26Ala, rs1139916), and GABRQ-I478F (Ile26Phe, rs3810651), in 200 patients with familial ET and 250 healthy controls using TaqMan genotyping. GABRA4-L26M, GABRE-S102A, and GABRQ-I478F genotype and allelic frequencies did not differ significantly between patients with ET and controls, and were unrelated to the age at onset of tremor or sex.

Gamma-aminobutyric acid (GABA) receptor rho (GABRR) polymorphisms and risk for essential tremor.

Some clinical and experimental data suggest a possible role of gamma-aminobutyrate (GABA)-ergic mechanisms in the pathophysiology of essential tremor (ET), such as the improvement of ET with some GABAergic drugs and the development of an experimental model of ET in GABA A receptor alpha-1 knockout mice (postural and kinetic tremor and motor incoordination similar to human ET). To investigate the possible association between the GABA receptor subtype rho1, rho2, and rho3 (GABRR1, GABRR2, and GABRR3) genotypes and allelic variants of the single nucleotide polymorphisms GABRR1-M26V (Met26Val, rs12200969), GABRR1-H27R (His26Arg, rs1186902), GABRR2-T455M (Thr55Met, rs282129), and GABRR3-Y205X (Tyr205X, rs832032), and the risk for ET, we studied the frequency of the previously mentioned GABRR genotypes and allelic variants in 200 patients with ET and 250 healthy controls using TaqMan genotyping. The frequencies of the GABBR1 genotypes and allelic variants of the studied polymorphisms did not differ significantly between patients with ET and controls, and were unrelated with the age at onset of tremor, gender, localization of tremor, and response of tremor to ethanol.

Dopamine receptor D3 (DRD3) genotype and allelic variants and risk for essential tremor.

To investigate the possible association between dopamine receptor D3 genotype (DRD3) and allelic variants and the risk for developing essential tremor (ET). Leukocytary DNA from 201 patients with ET and 282 healthy controls was studied for the genotype DRD3 and the occurrence of DRD3 allelic variants by using allele-specific PCR amplification and MslI-RFLP's analyses. A meta-analysis of previous studies was performed.

The nonsynonymous Thr105Ile polymorphism of the histamine N-methyltransferase is associated to the risk of developing essential tremor.

Objective: We analyzed in patients with essential tremor (ET) the Thr105Ile polymorphism of the Histamine N-methyltransferase (HNMT) enzyme that is associated to Parkinson's disease (PD) risk.

Methods: Leukocytary DNA from 204 ET patients and a control group of 295 unrelated healthy individuals was studied for the nonsynonymous HNMT Thr105Ile polymorphism by using amplification-restriction analyses.

Results: Patients with ET showed a higher frequency of homozygous HNMT 105Thr genotypes leading to high metabolic activity (p < 0.

Alcohol dehydrogenase 2 genotype and allelic variants are not associated with the risk for essential tremor.

Objective: To investigate the possible association between alcohol dehydrogenase 1B, beta-polypeptide (ADH2) genotype and allelic variants and the risk for developing essential tremor (ET).

Methods: Leukocytary DNA from 204 ET patients and 200 healthy controls was studied for the genotype ADH2 and the occurrence of ADH2 allelic variants using allele-specific polymerase chain reaction amplification and MslI-restriction fragment length polymorphism's analyses.

Results: The frequencies of the ADH2*1/ADH2*2 genotype and of the allelic variant ADH2*2 did not differ significantly in ET patients when compared with those of the controls.

Changes at the CYP2C locus and disruption of CYP2C8/9 linkage disequilibrium in patients with essential tremor.

To identify low-penetrance genes related to sporadic essential tremor (ET) at the CYP2C locus, located in chromosome 10 q23.33. Leukocytary DNA from 200 ET patients and a control group of 300 unrelated healthy individuals with known CYP2C19 genotypes was studied for common CYP2C8 and CYP2C9 allelic variants by using amplification-restriction analyses.

Environmental risk factors for essential tremor.

We conducted a case-control study searching for a possible role of environment in the risk of essential tremor (ET). We interviewed 142 ET patients and 284 age- and sex-matched controls about a family history of ET, exposure to environmental products containing lead, mercury, manganese, solvents and beta-carbolines, and exposure to agricultural work, well water, pesticides, and cigarette smoking and alcohol drinking habits. In a univariate study, reported family history of ET and exposure to agricultural work, pesticides, smelting, frosted glass, paintings, wheat, corn, and barley were more frequent in the ET patient group.

CYP2C19 polymorphism and risk for essential tremor.

Many patients with essential tremor (ET) develop acute adverse effects to primidone. We investigated the association between CYP2C19 polymorphism (possibly related to primidone metabolism) and the risk for developing essential ET and acute adverse effects to primidone. Leukocytary DNA from 200 ET patients and 300 healthy controls was studied for the genotype CYP2C19 and the occurrence of CYP2C19 allelic variants by using allele-specific PCR amplification and Sma I and BamH I RFLP analyses.

Drug-induced myoclonus: frequency, mechanisms and management.

Myoclonus is a sudden, abrupt, brief, 'shock-like' involuntary movement caused by muscular contractions ('positive myoclonus') or a sudden brief lapse of muscle contraction in active postural muscles ('negative myoclonus' or 'asterixis'). Various disorders can cause myoclonus including neurodegenerative and systemic metabolic disorders and CNS infections. In addition, myoclonus has been described as an adverse effect of some drugs.