Long-Term Effects of Alemtuzumab on CD4+ Lymphocytes in Multiple Sclerosis Patients: A 72-Month Follow-Up.

Introduction: Alemtuzumab is highly effective in the treatment of patients with relapsing multiple sclerosis (PwRMS) and selectively targets the CD52 antigen, with a consequent profound lymphopenia, particularly of CD4+ T lymphocytes. However, the immunological basis of its long-term efficacy has not been clearly elucidated.

Methods: We followed up 29 alemtuzumab-treated RMS patients over a period of 72 months and studied the immunological reconstitution of their CD4+ T cell subsets by means of phenotypic and functional analysis and through mRNA-related molecule expression, comparing them to healthy subject (HS) values (rate 2:1).

Source of medical information and behavioral seeking patterns in patients affected with Friedreich's ataxia and their caregivers: a survey study.

Background: Friedreich's ataxia (FRDA) is an untreatable disease that negatively impacts patients' and caregivers' quality of life.

Objectives: The aims were to improve the quality of the information for FRDA patients and caregivers and suggest a possible tool to spread this information.

Material And Methods: Thirty-four FRDA patients and 45 caregivers were interviewed separately using a structured self-administered survey about their information-seeking behavior, their level of expectation and satisfaction for the information received, and the need for further information.

Case Report: Covid-19 in Multiple Sclerosis Patients Treated With Ocrelizumab: A Case Series.

Limited data are available on the course of Coronavirus disease 2019 (COVID-19) in people with Multiple Sclerosis (MS). More real-world data are needed to help the MS community to manage MS treatment properly. In particular, it is important to understand the impact of immunosuppressive therapies used to treat MS on the outcome of COVID-19.

A real-world study of alemtuzumab in a cohort of Italian patients.

Background And Purpose: Real-world data on alemtuzumab are limited and do not provide evidence of its effectiveness after various disease-modifying therapies (DMTs). Our aim was to provide real-world data on the impact of clinical variables and previous DMTs on clinical response to alemtuzumab.

Methods: Sixteen Italian multiple sclerosis centers retrospectively included patients who started alemtuzumab from January 2015 to December 2018, and recorded demographics, previous therapies, washout duration, relapses, Expanded Disability Status Scale (EDSS) score, and magnetic resonance imaging data.

Family Functioning and Multiple Sclerosis: Study Protocol of a Multicentric Italian Project.

Multiple Sclerosis (MS) is a chronic inflammatory and neurodegenerative disease, which not only affects physical functioning, but is also associated with cognitive impairments and great psychological distress. The combination of those symptoms may have negative consequences on the family functioning of patients with MS, with detrimental effects on both marital relationships and parental bonding. Furthermore, the presence of individual characteristics and of an adequate social support may also contribute to the quality and endurance of family relationships.

Digital therapeutics in neurology.

Digital therapeutics (DTx) is a section of digital health defined by the DTx Alliance as "delivering evidence-based therapeutic interventions to patients that are driven by software to prevent, manage, or treat a medical disorder or disease. They are used independently or in concert with medications, devices, or other therapies to optimize patient care and health outcomes". Chronic disabling diseases could greatly benefit from DTx.

MRI activity and extended interval of Natalizumab dosing regimen: a multicentre Italian study.

Background: To minimize the risk of Progressive Multifocal Leukoencephalopathy and rebound in JCV-positive multiple sclerosis (MS) patients after 24 natalizumab doses, it has been proposed to extend the administrations interval. The objective is to evaluate the EID efficacy on MRI activity compared with the standard interval dosing (SID).

Methods: Observational, multicentre, retrospective cohort study, starting from the 24th natalizumab infusion to the loss of follow-up or 2 years after baseline.

Atypical Multiple Sclerosis Lesions or Progressive Multifocal Leukoencephalopathy Lesions: That Is the Question.

Progressive multifocal leukoencephalopathy (PML) is a serious infective disease of the central nervous system that may occur in case of severe immunosuppression or after some treatment for multiple sclerosis (MS) with natalizumab, dimethyl fumarate, and fingolimod. In these case reports, we highlight the importance of differential diagnosis between PML and MS lesions in order to provide rapidly the best treatment option, by discussing the finding of brain (magnetic resonance imaging) MRI suggestive for PML in 2 MS patients, one treated with dimethyl fumarate and the other during natalizumab withdrawal. In both cases, although brain MRI was highly suggestive for PML, the detection of John Cunningham virus-DNA copies in cerebrospinal fluid resulted in negative result.

The Meaning of Immune Reconstitution after Alemtuzumab Therapy in Multiple Sclerosis.

Alemtuzumab is a monoclonal antibody that binds to CD52, a protein present on the surface of mature lymphocytes, but not on the stem cells from which these lymphocytes are derived. It is currently used as an immune reconstitution therapy in patients with relapsing-remitting multiple sclerosis. Alemtuzumab treatment is an intermittent infusion that induces long-term remission of Multiple Sclerosis also in the treatment-free period.

Online Validation of a Battery of Questionnaires for the Assessment of Family Functioning and Related Factors.

Background: Family functioning relies on different factors that are related to the individual characteristics of each member, the social context in which the family nucleus is integrated, and the internal and interpersonal family factors. The Short Version of the Family Assessment Measure-III, Dyadic Adjustment Scale, Inventory of Parent and Peer Attachment, Twenty-item Toronto Alexithymia Scale, Hospital Anxiety and Depression Scale, and Multidimensional Scale of Perceived Social Support are among the most commonly employed self-report measures for the assessment of family functioning and related factors. Traditionally, these scales have been administered using paper-and-pencil versions.

The Adaptive Immune System in Multiple Sclerosis: An Estrogen-Mediated Point of View.

Multiple sclerosis (MS) is a chronic central nervous system inflammatory disease that leads to demyelination and neurodegeneration. The third trimester of pregnancy, which is characterized by high levels of estrogens, has been shown to be associated with reduced relapse rates compared with the rates before pregnancy. These effects could be related to the anti-inflammatory properties of estrogens, which orchestrate the reshuffling of the immune system toward immunotolerance to allow for fetal growth.

Extending the Interval of Natalizumab Dosing: Is Efficacy Preserved?

Extending the natalizumab interval after the 24th administration could reduce the risk of progressive multifocal leukoencephalopathy (PML). The objective is to evaluate the noninferiority of the efficacy of an extended interval dosing (EID) compared with the standard interval dosing (SID) of natalizumab. It is an observational, multicenter (14 Italian centers), retrospective cohort study, starting from the 24th natalizumab infusion to the loss of follow-up or 2 years after baseline.

Pregnancy Epigenetic Signature in T Helper 17 and T Regulatory Cells in Multiple Sclerosis.

Increasing evidence supports the anti-inflammatory role of estrogens in Multiple Sclerosis (MS), originating from the observation of reduction in relapse rates among women with MS during pregnancy, but the molecular mechanisms are still not completely understood. Using an integrative data analysis, we identified T helper (Th) 17 and T regulatory (Treg) cell-type-specific regulatory regions (CSR) regulated by estrogen receptor alpha (ERα). These CSRs were validated in polarized Th17 from healthy donors (HD) and in peripheral blood mononuclear cells, Th17 and Treg cells from relapsing remitting (RR) MS patients and HD during pregnancy.

Factors interfering with parenthood decision-making in an Italian sample of people with multiple sclerosis: an exploratory online survey.

Background: Little is known about the influence of multiple sclerosis (MS) diagnosis on parenthood attitude in people with MS (pwMS).

Objective: To investigate the impact of diagnosis, clinical features and external disease-related influences on parenthood decision-making in Italian pwMS.

Methods: A web-based survey was posted on SMsocialnetwork.

Botulinum toxin for Pisa syndrome: An MRI-, ultrasound- and electromyography-guided pilot study.

Introduction: Pisa syndrome is a disabling, medication-resistant, postural abnormality that may affect 7-10% of patients with Parkinson's disease. In this study, we sought to assess the efficacy of botulinum toxin injections in Parkinson's disease-associated Pisa syndrome using a Magnetic Resonance Imaging-, Ultrasonography-, and Electromyography-guided combined approach.

Methods: We conducted a pilot study to evaluate the efficacy of botulinum toxin type-A injection in paraspinal and non-paraspinal axial muscles after a Magnetic Resonance Imaging and ultrasound-guided electromyography evaluation.

Lack of CD4+ T cell percent decrease in alemtuzumab-treated multiple sclerosis patients with persistent relapses.

Alemtuzumab, a highly effective treatment for relapsing remitting multiple sclerosis (RRMS), induces lymphopenia especially of CD4+ T cells. Here, we report the atypical CD4+ T population behaviour of two patients with persistent disease activity despite repeated alemtuzumab treatments. Whereas lymphocytes count decreased and fluctuated accordingly to alemtuzumab administration, their CD4+ cell percentage was not or just mildly affected and was slightly below the lowest normal limit already before alemtuzumab.

Long-term safety evaluation of natalizumab for the treatment of multiple sclerosis.

Natalizumab is a humanized monoclonal antibody highly effective in relapsing-remitting multiple sclerosis (MS). Important concerns about its safety have been pointed out mainly because of the risk of progressive multifocal leukoencephalopathy (PML), caused by the opportunistic John-Cunningham virus (JCV). Areas covered: This review analyzes all the safety aspects related to the use and safety of natalizumab in MS patients.

Natalizumab in Multiple Sclerosis: Long-Term Management.

Natalizumab is a monoclonal antibody highly effective in the treatment of relapsing remitting multiple sclerosis (RRMS) patients. Despite its effectiveness, there are growing concerns regarding the risk of progressive multifocal leukoencephalopathy (PML), a brain infection caused by John Cunningham virus (JCV), particularly after 24 doses and in patients who previously received immunosuppressive drugs. Long-term natalizumab treated, immunosuppressive-pretreated, and JCV antibody-positive patients are asked to rediscuss natalizumab continuation or withdrawal after 24 doses.

Active CMV infection in two patients with multiple sclerosis treated with alemtuzumab.

Alemtuzumab is a humanized monoclonal antibody targeting the surface molecule CD52, resulting in a rapid depletion of innate and adaptive immune cells. Infection rates in multiple sclerosis (MS) treatment trials were higher in alemtuzumab than in interferon beta-treated patients. We report two MS patients who developed cytomegalovirus disease within 1 month after the first 5-day cycle of alemtuzumab.

Ultrasound-guided Botulinum Toxin-A Injections: A Method of Treating Sialorrhea.

Neurological diseases can be complicated by sialorrhea, an excessive flow of saliva. Patients suffering from moderate to severe sialorrhea have an impaired quality of life, often worsened by correlated complications such as aspiration pneumonia, oral infections, dental caries, and maceration of the skin. Diverse therapeutic approaches have been proposed for the treatment of sialorrhea, including surgery and the use of anticholinergic agents, with limited results and the possible occurrence of serious adverse events.

Alemtuzumab long-term immunologic effect: Treg suppressor function increases up to 24 months.

Objective: To analyze changes in T-helper (Th) subsets, T-regulatory (Treg) cell percentages and function, and mRNA levels of immunologically relevant molecules during a 24-month follow-up after alemtuzumab treatment in patients with relapsing-remitting multiple sclerosis (RRMS).

Methods: Multicenter follow-up of 29 alemtuzumab-treated patients with RRMS in the Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) I and CARE-MS II trials. Peripheral blood (PB) samples were obtained at months 0, 6, 12, 18, and 24.

Long-term follow-up of ultrasound-guided botulinum toxin-A injections for sialorrhea in neurological dysphagia.

Literature provides reports only of a limited follow-up single injection of botulinum toxin-A (BoNT-A) in patients with sialorrhea. The aim of our study is to evaluate the long-lasting efficacy and safety of ultrasound-guided BoNT-A injections for severe sialorrhea secondary to neurological dysphagia. We enrolled 38 severe adult sialorrhea patients referred consecutively to the neurology unit and performed bilateral parotid and submandibular gland BoNT-A injections under ultrasound guidance.

Epigenetic therapy for Friedreich ataxia.

Objective: To investigate whether a histone deacetylase inhibitor (HDACi) would be effective in an in vitro model for the neurodegenerative disease Friedreich ataxia (FRDA) and to evaluate safety and surrogate markers of efficacy in a phase I clinical trial in patients.

Methods: We used a human FRDA neuronal cell model, derived from patient induced pluripotent stem cells, to determine the efficacy of a 2-aminobenzamide HDACi (109) as a modulator of FXN gene expression and chromatin histone modifications. FRDA patients were dosed in 4 cohorts, ranging from 30mg/day to 240mg/day of the formulated drug product of HDACi 109, RG2833.