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Multiple Sclerosis

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By Alexandros Tsichlakis Medical representative
E D'Amico, A Zanghì, M Sciandra, G Borriello, G Callari, A Gallo, G Salemi, S Cottone, M Buccafusca, P Valentino, R B Bossio, L M E Grimaldi, C Pozzilli, G Tedeschi, M Zappia, F Patti
BACKGROUND: Teriflunomide (TRF) and Dimethyl fumarate (DMF) are licensed drugs for relapsing-remitting Multiple Sclerosis (RRMS). OBJECTIVES: We aimed to compare the rate and the time to discontinuation among persons with RRMS (pwRRMS), newly treated with TRF and DMF. MATERIALS AND METHODS: A retrospective study on prospectively collected data was performed in nine tertiary MS centers, in Italy. The 24-month discontinuation rate in the two cohorts was the primary study outcome...
December 4, 2018: Journal of Neurology
Tokunori Ikeda, Tatsuyuki Kakuma, Mari Watari, Yukio Ando
Here, we determined whether degree of decreased heart rate due to fingolimod treatment correlates with decreasing degree of lymphocytes in relapse-remitting multiple sclerosis (RRMS). In total, 30 patients with RRMS were treated with 0.5 mg fingolimod and their heart rate recorded every 30 minutes for 24 hours. Time trends of heart rate were characterised as three individual amplitudes and phase angles from three cosine curves using a mixed-effect model. Spearman's correlation coefficient and regression analysis were used to determine the effect of heart rate information on change in lymphocyte count pre- and post-fingolimod treatment...
November 6, 2018: Scientific Reports
Jae-Won Hyun, Yeseul Kim, Gayoung Kim, Su-Hyun Kim, Ho Jin Kim
Alemtuzumab is a potent monoclonal CD52 antibody used to treat patients with multiple sclerosis (MS). However, recent literature reports have described paradoxical activation of B cell-mediated disease within 1 year of the first cycle of alemtuzumab. We raise awareness that severe B cell-mediated disease activation could develop, even after two cycles of alemtuzumab, in some vulnerable MS patients; therefore, individualized therapeutic strategies should be considered in clinical practice. We also propose that a novel regulatory B-cell subset may be a candidate for a predictive biomarker of disease activation in MS patients treated with alemtuzumab...
November 7, 2018: Multiple Sclerosis: Clinical and Laboratory Research
G T Maniscalco, I Cerillo, G Servillo, M Napolitano, G Guarcello, V Abate, G Improta, C Florio
Alemtuzumab is a monoclonal antibody targeting the CD52 antigen used in the treatment of relapsing-remitting multiple sclerosis (RRMS). CD52 is expressed by lymphocytes and monocytes but less by neutrophils and not by platelets. We present a case of a 38-year-old woman with RRMS who developed early neutropenia with thrombocytopenia after alemtuzumab infusion. She had no fever or symptoms of infection or purpura. After two weeks her haematological disorders spontaneously resolved. We reported the first case of neutropenia and thrombocytopenia as a possible event occurring after alemtuzumab infusion in MS patients, even if in a mild grade...
December 2018: Clinical Neurology and Neurosurgery
M Pisa, P Della Valle, A Coluccia, V Martinelli, G Comi, A D'Angelo, L Moiola
Alemtuzumab is a highly effective monoclonal antibody for the treatment of multiple sclerosis (MS). During the immune reconstitution following the use of this treatment severe secondary autoimmune diseases (SADs) can develop. We present the case of a patient affected by active MS who failed to achieve disease control with several disease-modifying drugs and was thereafter successfully treated with alemtuzumab, obtaining no evidence of disease activity and a high quality of life. Twenty months after the first infusion of alemtuzumab the patient developed acquired haemophilia A (AHA), a treatable but potentially lifethreatening condition that should be considered a possible SADs associated to this drug...
November 29, 2018: Multiple Sclerosis and related Disorders
William Beattie, Bernard Yan, Siddharth Sood
Alemtuzumab is a monoclonal antibody used as a disease modifying agent in relapsing and remitting multiple sclerosis. It has not previously been associated with drug induced liver injury. Here we present a case of a 49 year old female developing drug induced liver injury secondary to alemtuzumab, confirmed upon rechallenge. Our patient developed severe hepatitis within two days of starting alemtuzumab, both initially and upon rechallenge. The alanine aminotransferase peaked at 577 units per litre and 426 units per litre after initial dose of alemtuzumab and rechallenge respectively...
October 19, 2018: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
A G Vakrakou, D Tzanetakos, S Valsami, E Grigoriou, K Psarra, J Tzartos, M Anagnostouli, E Andreadou, M E Evangelopoulos, G Koutsis, C Chrysovitsanou, E Gialafos, A Dimitrakopoulos, L Stefanis, C Kilidireas
BACKGROUND: Alemtuzumab has been demonstrated to reduce the risks of relapse and accumulation of sustained disability in Multiple Sclerosis (MS) patients compared to β-interferon. It acts against CD52, leading primarily to lymphopenia. Recent data have shown that mild neutropenia is observed in 16% of treated MS-patients whereas severe neutropenia occurred in 0.6%. CASE PRESENTATION: Herein, we present the case of a 34-year-old woman with relapsing-remitting MS, with a history of treatment with glatiramer acetate and natalizumab, who subsequently received Alemtuzumab (12 mg / 24 h × 5 days)...
October 29, 2018: BMC Neurology
B Mark Hoffman, Nuhad Abou Zeid, Umar Alam, James B Caress
BACKGROUND: Alemtuzumab administration is known to cause secondary autoimmune disease but has not been associated with the development of neurologic autoimmune conditions. Lambert-Eaton myasthenic syndrome (LEMS) is caused by autoantibodies directed against calcium channels on the neuromuscular junction. CASE REPORT: We report a case of a patient with relapsing-remitting multiple sclerosis (RRMS) treated with alemtuzumab who develop generalized weakness initially attributed to progression of MS but eventually determined to be due to LEMS...
October 22, 2018: Multiple Sclerosis and related Disorders
Maria Pia Sormani, Nicola De Stefano, Gavin Giovannoni, Dawn Langdon, Daniela Piani-Meier, Dieter A Haering, Ludwig Kappos, Davorka Tomic
OBJECTIVE: To assess the prognostic value of practice effect on Paced Auditory Serial Addition Test (PASAT) in multiple sclerosis. METHODS: We compared screening (day -14) and baseline (day 0) PASAT scores of 1009 patients from the FTY720 Research Evaluating Effects of Daily Oral therapy in Multiple Sclerosis (FREEDOMS) trial. We grouped patients into high and low learners if their PASAT score change was above or below the median change in their screening PASAT quartile group...
October 15, 2018: Journal of Neurology, Neurosurgery, and Psychiatry
Robert Zivadinov, Jennie Medin, Nasreen Khan, Jonathan R Korn, Tanuja Chitnis, Robert T Naismith, Enrique Alvarez, Michael G Dwyer, Niels Bergsland, Ellen Carl, Diego Silva, Bianca Weinstock-Guttman
BACKGROUND: The effectiveness of fingolimod on clinical and magnetic resonance imaging (MRI) outcomes in patients with multiple sclerosis (MS) has been well established in trials and, to a lesser extent, in the real world. OBJECTIVE: To evaluate clinical and MRI outcomes in patients with relapsing MS receiving fingolimod in US clinical practice. METHODS: Clinical and MRI data from 590 patients initiating fingolimod treatment at 33 MS centers in the USA were retrospectively analyzed...
October 3, 2018: Multiple Sclerosis and related Disorders
Antonio Riccardo Buonomo, Francesco Saccà, Emanuela Zappulo, Federico De Zottis, Roberta Lanzillo, Ivan Gentile, Antonio Carotenuto, Guglielmo Borgia, Cinzia Valeria Russo
Alemtuzumab (a drug highly active in multiple sclerosis) is a humanized monoclonal antibody targeting the surface molecule CD52. It causes a rapid depletion of innate and adaptive immune cells with a peak during the first month after infusion. Infection rates in alemtuzumab-treated patients with multiple sclerosis in clinical trials were higher in than in interferon beta-treated patients. Cytomegalovirus (CMV) primary infections and reactivations have been reported in this setting of patients. We describe the case of a patient that developed both viral (CMV) and bacterial pneumonia one month after alemtuzumab infusion for multiple sclerosis...
October 2, 2018: Multiple Sclerosis and related Disorders
Jarrett Madeley, Georgina Hodges, Andrew Birchley
This case illustrates a 36-year-old man who presented with a factor VIII (FVIII) inhibitor (acquired haemophilia A) with cutaneous bleeding and a significant thigh haematoma. No traditional risk factors for the development of a FVIII inhibitor were identified. However, previous treatment with alemtuzumab for multiple sclerosis was noted in the patient's history. Alemtuzumab is an anti-CD52 monoclonal antibody and is known to be associated with the development of a number of autoimmune conditions, with a delay in onset of these conditions as long as 5 years after the cessation of treatment...
October 17, 2018: BMJ Case Reports
I J Chou, C F Kuo, R Tanasescu, C R Tench, C G Tiley, C S Constantinescu, W P Whitehouse
BACKGROUND AND PURPOSE: We aimed to determine the prevalence of epilepsy in patients with multiple sclerosis (MS) at diagnosis, the risk of developing epilepsy after the diagnosis of MS and the relative risk of mortality associated with epilepsy. METHODS: We used the UK Clinical Practice Research Data-link to identify 2526 patients with incident MS and 9980 age-, sex- and index year-matched non-MS controls from 1997 to 2006. Logistic regression was used to estimate odds ratios [95% confidence interval (CI)] for epilepsy and Cox regression was used to estimate hazard ratios (HRs) (95% CI) for epilepsy and mortality...
October 12, 2018: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
Evan Darwin, Paolo Romanelli, Hadar Lev-Tov
Multiple Sclerosis (MS) is a chronic autoimmune disease that presents with a wide variety of sensory and motor deficiencies. New medications targeting B cells have been approved to treat MS, but the side effect profile has not been widely explored. Herein, we report a case of drug-induced psoriasiform dermatitis following ocrelizumab treatment. Physicians should be cognizant of this possible side effect in patients receiving treatment for MS.
July 15, 2018: Dermatology Online Journal
J Lorscheider, J Kuhle, G Izquierdo, A Lugaresi, E Havrdova, D Horakova, R Hupperts, P Duquette, M Girard, A Prat, F Grand'Maison, P Grammond, P Sola, D Ferraro, M Trojano, C Ramo-Tello, J Lechner-Scott, E Pucci, C Solaro, M Slee, V Van Pesch, J L Sanchez Menoyo, A van der Walt, H Butzkueven, L Kappos, T Kalincik
BACKGROUND AND PURPOSE: Treatment options in primary progressive multiple sclerosis (PPMS) are scarce and, with the exception of ocrelizumab, anti-inflammatory agents have failed to show efficacy in ameliorating disability progression. The aim of this study was to investigate a potential effect of anti-inflammatory disease-modifying treatment on disability outcomes in PPMS. METHODS: Using MSBase, a large, international, observational database, we identified patients with PPMS who were either never treated or treated with a disease-modifying agent...
October 9, 2018: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
Mark D Willis, Ben Hope-Gill, Patrick Flood-Page, Fady Joseph, Ed Needham, Joanne Jones, Alasdair Coles, Neil P Robertson
Despite proven efficacy of alemtuzumab in multiple sclerosis (MS), approximately 50% of individuals will develop a new autoimmune disease following treatment. To date, these have largely been antibody mediated and organ specific (primarily affecting the thyroid gland). In a retrospective case series of 187 patients from two UK specialist centres (Cardiff and Cambridge) followed up for a median of 10 years, we report three (1.6%) cases of sarcoidosis following alemtuzumab treatment of MS. This report increases the spectrum of auto-inflammatory disease following alemtuzumab and should be considered by clinicians when using this therapeutic agent for MS...
November 2018: Multiple Sclerosis: Clinical and Laboratory Research
Jonas Graf, Marius Ringelstein, Klaudia Lepka, Jörg Schaller, Helmut Quack, Hans-Peter Hartung, Orhan Aktas, Philipp Albrecht
BACKGROUND: Understanding the long-term effect of alemtuzumab on the immune system of multiple sclerosis (MS) patients is crucial. OBJECTIVE: To report a case of acute sarcoidosis (Löfgren's syndrome) in a relapsing-remitting MS patient, 1.5 years after the second course of alemtuzumab treatment. CASE REPORT: Sarcoidosis was confirmed dermatohistologically, radiologically, and serologically. Analysis of the lymphocyte subpopulations showed a persistent effect of alemtuzumab treatment (CD4/CD8 ratio increased, absolute lymphocyte count of CD19-positive cells increased while CD3/4/8-positive cells were decreased)...
November 2018: Multiple Sclerosis: Clinical and Laboratory Research
Ursela Baber, Andrew Bouley, Emily Egnor, Jacob A Sloane
Rituximab, a monoclonal antibody to CD20, is an effective treatment for relapsing remitting multiple sclerosis (MS) reducing relapse rate by at least 50% over time. Although the mechanism for this clinical benefit is unclear, rituximab depletes circulating B cells, which can perform antigen presentation and stimulation of T cells. Another anti-CD20 drug, ocrelizumab, has recently been FDA approved to treat both relapsing remitting and progressive forms of MS. While long-term effects of ocrelizumab use are essentially unknown, long-term use of rituximab has been associated with the development of progressive multifocal leukoencephalopathy (PML) at an incidence of approximately 1/25,000 in non-MS conditions...
October 2018: Journal of Neurology
Paola Perini, Francesca Rinaldi, Marco Puthenparampil, Michela Marcon, Francesco Perini, Paolo Gallo
BACKGROUND: Dimethyl fumarate (DMF) is approved as first line therapy for relapsing-remitting multiple sclerosis (RRMS). In some (3%) patients, DMF induces a marked lymphopenia. Herpes simplex encephalitis (HSE) may occur in lymphopenic subjects under treatment with immune-suppressive drugs. CASE PRESENTATION: We report a case of a 39-year-old female patient with RRMS that developed HSE temporally associated with a marked and sudden drop in lymphocyte count, from 1200/µl to 600/µl, in the peripheral blood...
September 11, 2018: Multiple Sclerosis and related Disorders
Scott Otallah, Brenda Banwell
PURPOSE OF REVIEW: Diagnostic criteria for pediatric-onset multiple sclerosis (POMS) and related demyelinating disorders have been updated, neuroimaging studies have revealed new insights, biological assays identify patients with specific antibodies that influence both diagnosis and treatment, clinical trials are informing on treatment efficacy and safety, and longitudinal studies of neurological, cognitive and quality of life outcomes are informing on the impact of these diseases. We provide updates to assist providers caring for these children...
September 18, 2018: Current Neurology and Neuroscience Reports
2018-09-23 13:57:41
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