Kappa index in the diagnostic work-up of autoimmune encephalitis.

Background: The presence of inflammatory changes in the cerebrospinal fluid (CSF), including immunoglobulin intrathecal synthesis (IS), can support the diagnosis of autoimmune encephalitis (AE) and allow prompt treatment. The main aim of our study was to calculate the Kappa index as a marker of IS, in patients with AE.

Methods: Charts of patients undergoing a diagnostic work-up for suspected AE between 2009 and 2023 were reviewed and the Graus criteria applied.

Clinical, prognostic and pathophysiological implications of MOG-IgG detection in the CSF: the importance of intrathecal MOG-IgG synthesis.

Background: Cerebrospinal fluid myelin oligodendrocyte glycoprotein IgG (CSF MOG-IgG) are found in a proportion of patients with MOG antibody-associated disorder (MOGAD) and have been associated with severe disease presentations. However, most studies did not systematically investigate the role of MOG-IgG intrathecal synthesis (ITS).

Methods: We retrospectively studied 960 consecutive patients with paired serum and CSF samples screened for MOG-IgG using a live cell-based assays.

Modulation of Tregs and iNKT by Fingolimod in Multiple Sclerosis Patients.

The altered numbers and functions of cells belonging to immunoregulatory cell networks such as T regulatory (Tregs) and invariant Natural Killer T (iNKT) cells have been reported in Multiple Sclerosis (MS), an immune-mediated disease. We aimed to assess the frequencies of Tregs and iNKT cells in MS patients throughout a one-year treatment with fingolimod (FTY) and to correlate immunological data with efficacy and safety data. The percentage of Tregs (defined as Live Dead-CD3 + CD4 + FoxP3 + CD25++/CD127- cells) increased steadily throughout the year, while there was no significant difference in the absolute number or percentage of iNKT cells (defined as CD3 + CD14-CD19- Vα24-Jα18 TCR+ cells).

Mitochondrial damage-associated molecular patterns stimulate reactive oxygen species production in human microglia.

Microglia are the resident innate immune cells of the central nervous system and exert functions of host defense and maintenance of normal tissue homeostasis, along with support of neuronal processes in the healthy brain. Chronic and dysregulated microglial cell activation has increasingly been linked to the status of neuroinflammation underlying many neurodegenerative diseases, including multiple sclerosis (MS). However, the stimulus (or stimuli) and mechanisms by which microglial activation is initiated and maintained MS are still debated.

Increased plasma levels of mitochondrial DNA and pro-inflammatory cytokines in patients with progressive multiple sclerosis.

The role of damage-associated molecular patterns in multiple sclerosis (MS) is under investigation. Here, we studied the contribution of circulating high mobility group box protein 1 (HMGB1) and mitochondrial DNA (mtDNA) to neuroinflammation in progressive MS. We measured plasmatic mtDNA, HMGB1 and pro-inflammatory cytokines in 38 secondary progressive (SP) patients, 35 primary progressive (PP) patients and 42 controls.

Mitochondrial functionality and metabolism in T cells from progressive multiple sclerosis patients.

Patients with primary progressive (PP) and secondary progressive (SP) forms of multiple sclerosis (MS) exhibit a sustained increase in the number of Th1, T cytotoxic type-1 and Th17 cells in peripheral blood, suggesting that the progressive phase is characterized by a permanent peripheral immune activation. As T cell functionality and activation are strictly connected to their metabolic profile, we investigated the mitochondrial functionality and metabolic changes of T cell subpopulations in a cohort of progressive MS patients. T cells from progressive patients were characterized by low proliferation and increase of terminally differentiated/exhausted cells.

First-line disease-modifying drugs in relapsing-remitting multiple sclerosis: an Italian real-life multicenter study on persistence.

Objective: The introduction of oral disease-modifying drugs (DMDs) in addition to the available, injectable, ones for relapsing-remitting multiple sclerosis (RRMS) could be expected to improve medication persistence due to a greater acceptability of the route of administration. The aim of the study was to compare the proportion of patients discontinuing injectable DMDs (interferon beta 1a/1b, pegylated interferon, glatiramer acetate) with those discontinuing oral DMDs (dimethylfumarate and teriflunomide) during an observation period of at least 12 months. Secondary aims were to compare the time to discontinuation and the reasons for discontinuation between the two groups and to explore the demographic and clinical factors associated with DMD discontinuation.

Vulnerability to Infarction During Cerebral Ischemia in Migraine Sufferers.

Background And Purpose: Cerebral hyperexcitability in migraine experiencers might sensitize brain tissue to ischemia. We investigated whether a personal history of migraine is associated with vulnerability to brain ischemia in humans.

Methods: Multicenter cohort study of patients with acute ischemic stroke who underwent a brain computed tomography perfusion and were scheduled to undergo reperfusion therapy.

Systematic assessment and characterization of chronic pain in multiple sclerosis patients.

Pain is one of the most disabling clinical symptoms in patients with multiple sclerosis (MS). Several studies have already assessed the prevalence of pain in MS patients, reporting variable results, probably due to methodological differences. The aim of this single-centre cross-sectional study was to define the prevalence and characteristics of chronic pain in a population of MS patients using validated tools, and to analyse these data in relation to demographic and clinical features, including disease duration and disability (EDSS and its single functional system scores).

Definitive childlessness in women with multiple sclerosis: a multicenter study.

The frequency of definitive childlessness in women with multiple sclerosis (MS) may be higher than in the general population. MS may also affect decisions on the delivery procedure and on breast-feeding issues. Aim of the study was to assess the frequency of childlessness and its possible causes, the proportion of cesarean deliveries (CD), and the frequency of breast-feeding in patients and controls who have reached the end of their reproductive period.

A multicenter study on the diagnostic significance of a single cerebrospinal fluid IgG band.

The analysis of paired cerebrospinal fluid (CSF) and serum samples with isolectric focusing (IEF) can yield different patterns which can be of aid in the differential diagnosis of central nervous system (CNS) disorders. Rarely, a single CSF-restricted IgG band, which is not included within these patterns, can be detected in association with inflammatory disorders, multiple sclerosis (MS) above all. However, the diagnostic meaning of this abnormality is still uncertain.

Association Between Migraine and Cervical Artery Dissection: The Italian Project on Stroke in Young Adults.

Importance: Although sparse observational studies have suggested a link between migraine and cervical artery dissection (CEAD), any association between the 2 disorders is still unconfirmed. This lack of a definitive conclusion might have implications in understanding the pathogenesis of both conditions and the complex relationship between migraine and ischemic stroke (IS).

Objective: To investigate whether a history of migraine and its subtypes is associated with the occurrence of CEAD.

Invariant natural killer T cells and mucosal-associated invariant T cells in multiple sclerosis.

Multiple sclerosis (MS) is a chronic progressive inflammatory demyelinating disorder of the central nervous system, and in several countries is a leading cause of permanent neurological disability in young adults, particularly women. MS is considered an autoimmune disease, caused by an aberrant immune response to environmental triggers in genetically susceptible subjects. However, the contribution of the innate or of the adaptive immune system to the development and progression of the disease has not yet been fully elucidated.

iNKT Cells in Secondary Progressive Multiple Sclerosis Patients Display Pro-inflammatory Profiles.

Background: Multiple sclerosis (MS), an autoimmune disease with neurodegeneration and inflammation is characterized by several alterations of different T cell subsets. However, few data exist on the role of iNKT lymphocytes.

Objective: To identify possible changes in the phenotype of iNKT cells in patients with different clinical forms of MS and find alterations in their polyfunctionality [i.

Cerebrospinal fluid anti-Epstein-Barr virus specific oligoclonal IgM and IgG bands in patients with clinically isolated and Guillain-Barré syndrome.

Epstein-Barr virus (EBV) has been implicated in multiple sclerosis (MS) pathogenesis. We aimed to assess the frequency of EBV-specific IgG and IgM oligoclonal bands (OCB) in cerebrospinal fluid (CSF) of 50 patients with clinically isolated syndrome (CIS) and in 27 controls with Guillain-Barré syndrome (GBS). Furthermore, we assessed correlations between the presence of OCB and CIS patients' CSF, MRI, and clinical variables.

Risk Profile of Symptomatic Lacunar Stroke Versus Nonlobar Intracerebral Hemorrhage.

Background And Purpose: Although lacunar stroke (LS) and deep intracerebral hemorrhage (dICH) represent acute manifestations of the same pathological process involving cerebral small vessels (small vessel disease), it remains unclear what factors predispose to one phenotype rather than the other at individual level.

Methods: Consecutive patients with either acute symptomatic LS or dICH were prospectively enrolled as part of a multicenter Italian study. We compared the risk factor profile of the 2 subgroups using multivariable logistic regression.

Methylprednisolone-induced Toxic Hepatitis After Intravenous Pulsed Therapy for Multiple Sclerosis Relapses.

High-dose, intravenous methylprednisolone (MP) is the only recommended first-line treatment for multiple sclerosis relapses. However, there are increasing reports on liver toxicity induced by this treatment regimen. We report of 4 multiple sclerosis patients with no history of viral/metabolic liver disorders or alcohol/hepatotoxic drug intake, who developed hypertransaminasaemia following intravenous MP.

Cerebrospinal fluid CXCL13 in clinically isolated syndrome patients: Association with oligoclonal IgM bands and prediction of Multiple Sclerosis diagnosis.

Cerebrospinal fluid (CSF) CXCL13 was shown to correlate with markers of intrathecal inflammation and CSF oligoclonal IgM bands (IgMOB) have been associated with a more severe Multiple Sclerosis (MS) course. We correlated CSF CXCL13 levels with clinical, MRI and CSF parameters, including CSF IgMOB, in 110 Clinically Isolated Syndrome (CIS) patients. CSF CXCL13 levels correlated with CSF cell count, total protein, IgG Index and with the presence of CSF IgGOB and IgMOB.

Determinants of premature familial arterial thrombosis in patients with juvenile ischaemic stroke. The Italian Project on Stroke in Young Adults (IPSYS).

Factors predicting family history (FH) of premature arterial thrombosis in young patients with ischaemic stroke (IS) have not been extensively investigated, and whether they might influence the risk of post-stroke recurrence is still unknown. In the present study we analysed 1,881 consecutive first-ever IS patients aged 18-45 years recruited from January 2000 to January 2012 as part of the Italian Project on Stroke in Young Adults (IPSYS). FH of premature arterial thrombosis was any thrombotic event [IS, myocardial infarction or other arterial events event] < 45 years in proband's first-degree relatives.

Previous treatment influences fingolimod efficacy in relapsing-remitting multiple sclerosis: results from an observational study.

Objective: Fingolimod (FTY) is licensed as a disease-modifying treatment in highly active relapsing-remitting multiple sclerosis. The aim of the study was to evaluate the efficacy and safety of FTY in a real-life setting and to explore the possible role of clinical and MRI parameters, including previous treatment type, in predicting its efficacy.

Methods: Clinical and MRI data was collected on 127 patients assigned to treatment with FTY in six multiple sclerosis centers in Emilia-Romagna, Italy, between August 2011 and June 2013.

Predictors of long-term recurrent vascular events after ischemic stroke at young age: the Italian Project on Stroke in Young Adults.

Background: Data on long-term risk and predictors of recurrent thrombotic events after ischemic stroke at a young age are limited.

Methods And Results: We followed 1867 patients with first-ever ischemic stroke who were 18 to 45 years of age (mean age, 36.8±7.