Ultrastructural Characterization of PBMCs and Extracellular Vesicles in Multiple Sclerosis: A Pilot Study.

Growing evidence identifies extracellular vesicles (EVs) as important cell-to-cell signal transducers in autoimmune disorders, including multiple sclerosis (MS). If the etiology of MS still remains unknown, its molecular physiology has been well studied, indicating peripheral blood mononuclear cells (PBMCs) as the main pathologically relevant contributors to the disease and to neuroinflammation. Recently, several studies have suggested the involvement of EVs as key mediators of neuroimmune crosstalk in central nervous system (CNS) autoimmunity.

Multi-Criterial Model for Weighting Biological Risk Factors in Multiple Sclerosis: Clinical and Health Insurance Implications.

The etiology of Multiple Sclerosis (MS) remains undetermined. Its pathogenic risk factors are thought to play a negligible role individually in the development of the disease, instead assuming a pathogenic role when they interact with each other. Unfortunately, the statistical weighting of this pathogenic role in predicting MS risk is currently elusive, preventing clinical and health insurance applications.

Fluphenazine-Induced Neurotoxicity with Acute Almost Transient Parkinsonism and Permanent Memory Loss: Lessons from a Case Report.

We report the singular case of a 31-year-old woman who developed very serious Fluphenazine-induced parkinsonism over a few days due to a doubly incongruent drug prescription by indication and dosage having been applied to a healthy subject over one week instead of seven months. Unlike gradual drug-induced parkinsonism, our patient experienced acute extrapyramidal syndrome (EPS), reaching significant motor and sphincter disability in just a few days, followed by a gradual incomplete recovery over more than six months. In fact, after drug discontinuation, hypomimia and slight left hemi-somatic rigidity with bradykinesia remained, as well as stable non-progressive memory disturbances.

Changes in Brain Volumes Are Relevant during Natalizumab-Associated Progressive Multifocal Leukoencephalopathy: Lessons from a Case Report.

This is a case report concerning a Natalizumab-associated Progressive Multifocal Leukoencephalopathy (PML) with cerebellar localization and wakefulness disturbances. Awakening and clinical improvement dramatically occurred as soon as the immune reconstitution inflammatory syndrome (IRIS) took place, being it mild in nature and colocalizing with the PML lesion. In these ideal experimental conditions, we applied brain magnetic resonance imaging post-analysis in order to know changes in brain volumes underlying the pathological process over the infection period.

Dementia-Associated Compulsive Singing (DACS): Presentation of Unpublished Clinical Cases Miniseries.

Dementia-associated compulsive singing (DACS) is a neurotransmettitorial-based behavioral disturbance, characterized by an unabating melodic expression, occurring in patients that suffer from evolved dementia. Previously described only as a "punding" aspect of the dopamine dysregulation syndrome (DDS) in the Parkinson's disease (PD), compulsive singing has now been described, for the first time, in four non-PD patients effectively treated with Haloperidol or Quetiapine. Unlike the DDS-associated conditions, in our cases DACS is not pharmacologically induced, being that all patients were L-dopa-free.

GANAB and -Glycans Substrates Are Relevant in Human Physiology, Polycystic Pathology and Multiple Sclerosis: A Review.

Glycans are one of the four fundamental macromolecular components of living matter, and they are highly regulated in the cell. Their functions are metabolic, structural and modulatory. In particular, ER resident -glycans participate with the GlcManGlcNAc highly conserved sequence, in protein folding process, where the physiological balance between glycosylation/deglycosylation on the innermost glucose residue takes place, according GANAB/UGGT concentration ratio.

IFP35 Is a Relevant Factor in Innate Immunity, Multiple Sclerosis, and Other Chronic Inflammatory Diseases: A Review.

Discovered in 1993 by Bange et al., the 35-kDa interferon-induced protein (IFP35) is a highly conserved cytosolic interferon-induced leucine zipper protein with a 17q12-21 coding gene and unknown function. Belonging to interferon stimulated genes (ISG), the IFP35 reflects the type I interferon (IFN) activity induced through the JAK-STAT phosphorylation, and it can homodimerize with N-myc-interactor (NMI) and basic leucine zipper transcription factor (BATF), resulting in nuclear translocation and a functional expression.

GANAB as a Novel Biomarker in Multiple Sclerosis: Correlation with Neuroinflammation and IFI35.

Multiple sclerosis (MS) still lacks reliable biomarkers of neuroinflammation predictive for disease activity and treatment response. Thus, in a prospective study we assessed 55 MS patients (28 interferon (IFN)-treated, 10 treated with no-IFN therapies, 17 untreated) and 20 matched healthy controls (HCs) for the putative correlation of the densitometric expression of glucosidase II alpha subunit (GANAB) with clinical/paraclinical parameters and with interferon-induced protein 35 (IFI35). We also assessed the disease progression in terms of the Rio Score (RS) in order to distinguish the responder patients to IFN therapy (RS = 0) from the non-responder ones (RS ≥ 1).

Early-Life Exposure to Environmental Air Pollution and Autism Spectrum Disorder: A Review of Available Evidence.

The number of children diagnosed with Autism Spectrum Disorder (ASD) has rapidly increased globally. Genetic and environmental factors both contribute to the development of ASD. Several studies showed linkage between prenatal, early postnatal air pollution exposure and the risk of developing ASD.

The Age-Related Efficacy of Dimethyl Fumarate and Natalizumab in the Real-World Management of Multiple Sclerosis.

We investigated the comparative age-related efficacy of dimethyl fumarate (DMF) and natalizumab (NTZ) in clinical practice on multiple sclerosis (MS). Research in this area is lacking in the previous literature. In a three-year retrospective and clinical-paraclinical study, we compared 173 DMF patients and 94 NTZ patients with a similar average age (40 years) and disease duration (DD) (10 years).

The influence of lifestyle factors on miRNA expression and signal pathways: a review.

The term 'lifestyle' includes different factors that contribute to the maintenance of a good health status. Increasing evidences suggest that lifestyle factors may influence epigenetic mechanisms, such as miRNAs expression. The dysregulation of miRNAs can modify the expression of genes and molecular pathways that may lead to functional alterations.

IFI35 as a biomolecular marker of neuroinflammation and treatment response in multiple sclerosis.

Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) with unpredictable clinical outcome. As such, there is an urgent need to identify biomarkers that can predict the treatment response. Therefore, in an open-label, clinical, paraclinical and molecular prospective study, we assessed 50 interferon (IFN) treated MS patients for Rio Score (RS)/Modified Rio Score (MRS) and densitometric expression of the interferon-induced protein 35 (IFI35), a signal-protein with potential to be clinically relevant in the management of the disease.

Progressive familial intrahepatic cholestasis type-3 and multiple sclerosis: lessons from comorbidity.

The comorbidity between multiple sclerosis (MS) and progressive familial intrahepatic cholestasis type-3 (PFIC3) has never been described yet. ABCB4 gene encodes the multidrug resistant protein 3 (MDR3) and its mutations induce PFIC3 as well as intrahepatic cholestasis of pregnancy (ICP) and drug-induced liver injury (DILI). We describe the case of a 32-year-old female with MS and PFIC3 who was effectively treated with natalizumab and ursodeoxycholic acid (UCDA), in contrast to glatiramer acetate, dimethylfumarate, and IFNb1a associated with DILI.

Metastases of Hepatocellular Carcinoma Misdiagnosed as Isolated Hypertrophic Cardiomyopathy.

At present, cardiac metastasis of hepatocellular carcinoma is rarely mentioned in the literature. We report a hepatocellular carcinoma patient with cardiac metastasis misdiagnosed as hypertrophic cardiomyopathy in 2011. Two years later, on presentation of syncope, an abnormal ventricular septal size was recorded by ultrasound scan, and was subsequently shown by magnetic resonance imaging to be a tumour lesion.

Transbulbar B-Mode Sonography in Multiple Sclerosis: Clinical and Biological Relevance.

Optic nerve sheath diameter quantification by transbulbar B-mode sonography is a recently validated technique, but its clinical relevance in relapse-free multiple sclerosis patients remains unexplored. In an open-label, comparative, cross-sectional study, we aimed to assess possible differences between patients and healthy controls in terms of optic nerve sheath diameter and its correlation with clinical/paraclinical parameters in this disease. Sixty unselected relapse-free patients and 35 matched healthy controls underwent transbulbar B-mode sonography.

Dramatic recovery of steroid-refractory relapsed multiple sclerosis following Fingolimod discontinuation using selective immune adsorption.

Background: Selective immune adsorption (SIA) is an emerging method for treating immune-mediated neurological diseases, given its superior safety profile compared to plasma exchange (PEX). However, the available literature concerning Multiple Sclerosis includes no cases of SIA applied to steroid-refractory rebound after Fingolimod discontinuation.

Case Presentation: Here we report the case of a 32-year-old woman suffering from multiple sclerosis treated with Fingolimod and admitted to a Multiple Sclerosis Centre after drug discontinuation due to the occurrence of lymphopenia.

The clinical potential of blood-proteomics in multiple sclerosis.

Background: The aetiology of multiple sclerosis (MS) remains unknown. This hampers molecular diagnosis and the discovery of bio-molecular markers. Consequently, MS diagnostic procedures are complex and criteria for assessing therapeutic efficacy are controversial, suggesting that a pathophysiological rather than an aetiological approach to the disease would be more appropriate.

Clinical and audiological follow up of a family with the 8363G>A mutation in the mitochondrial DNA.

Hearing loss is relatively common in mtDNA-related disorders. While auditory function has been assessed fully in the syndrome of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes, few studies have investigated the degree of progressive hearing deficit in individuals bearing other mtDNA mutations. We performed a 4-year clinical and audiological follow up in a family carrying the 8363G>A mutation in the mitochondrial transfer ribonucleic acid lysine (tRNA(Lys)) gene who displayed a progressive neuromuscular disease.

Hearing impairment in congenital diaphragmatic hernia: the inaudible and noiseless foot of time.

Aim Of The Study: Infants with congenital diaphragmatic hernia (CDH) are at high risk of sensorineural hearing loss (SNHL). Extracorporeal membrane oxygenation is known to increase this risk, but little is known about other potential causes. We evaluated the impact of several risk factors on SNHL development in CDH survivors not treated with extracorporeal membrane oxygenation.

Effect of intravenous methylprednisolone on the number, size and confluence of plaques in relapsing-remitting multiple sclerosis.

The aim of the present study was to evaluate whether intravenous methylprednisolone (IVMP) pulses affect the confluence and enlargement of T2 lesions in the long term in patients with relapsing-remitting (RR) multiple sclerosis (MS). Of 88 RR MS patients, randomly assigned to regular pulses of IVMP (1 g/day for 5 days with an oral prednisone taper) or IVMP on the same dose schedule only for relapses, and followed up without other disease-modifying drug therapy for 5 years, 81 patients completed the trial as planned. Pulsed IVMP was given every 4 months for 3 years, and then every 6 months for the subsequent 2 years.