scholarly journals Autoimmune Encephalitis and CSF Anti-GluR3 Antibodies in an MS Patient after Alemtuzumab Treatment

2019 ◽  
Vol 9 (11) ◽  
pp. 299 ◽  
Author(s):  
Maria Chiara Buscarinu ◽  
Arianna Fornasiero ◽  
Giulia Pellicciari ◽  
Roberta Reniè ◽  
Anna Chiara Landi ◽  
...  
Keyword(s):  
Cognitive Deficits ◽  
Focal Epilepsy ◽  
Brain Magnetic Resonance Imaging ◽  
Autoimmune Encephalitis ◽  
Complete Recovery ◽  
Neurological Status ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Serial Brain

A 45-year-old Italian woman, affected by relapsing–remitting multiple sclerosis (RR-MS) starting from 2011, started treatment with alemtuzumab in July 2016. Nine months after the second infusion, she had an immune thrombocytopenic purpura (ITP) with complete recovery after steroid treatment. Three months after the ITP, the patient presented with transient aphasia, cognitive deficits, and focal epilepsy. Serial brain magnetic resonance imaging showed a pattern compatible with encephalitis. Autoantibodies to glutamate receptor 3 peptide A and B were detected in cerebrospinal fluid and serum, in the absence of any other diagnostic cues. After three courses of intravenous immunoglobulin (0.4 mg/kg/day for 5 days, 1 month apart), followed by boosters (0.4 mg/kg/day) every 4–6 weeks, her neurological status improved and is currently comparable with that preceding the encephalitis. Autoimmune complications of the central nervous system during alemtuzumab therapy are relatively rare: only one previous case of autoimmune encephalitis following alemtuzumab treatment has been reported to date.

scholarly journals The STING-IFN-β-Dependent Axis Is Markedly Low in Patients with Relapsing-Remitting Multiple Sclerosis

2020 ◽  
Vol 21 (23) ◽  
pp. 9249
Author(s):  
Lars Masanneck ◽  
Susann Eichler ◽  
Anna Vogelsang ◽  
Melanie Korsen ◽  
Heinz Wiendl ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Type I ◽  
Autoimmune Encephalomyelitis ◽  
Beneficial Effects ◽  
Endogenous Production ◽  
Relapsing Remitting ◽  
Peripheral Lymphoid Tissue ◽  
The Central Nervous System ◽  
Peripheral Immune Cells ◽  
Relapsing Remitting Multiple Sclerosis

Cyclic GMP-AMP-synthase is a sensor of endogenous nucleic acids, which subsequently elicits a stimulator of interferon genes (STING)-dependent type I interferon (IFN) response defending us against viruses and other intracellular pathogens. This pathway can drive pathological inflammation, as documented for type I interferonopathies. In contrast, specific STING activation and subsequent IFN-β release have shown beneficial effects on experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS). Although less severe cases of relapse-remitting MS (RRMS) are treated with IFN-β, there is little information correlating aberrant type I IFN signaling and the pathologic conditions of MS. We hypothesized that there is a link between STING activation and the endogenous production of IFN-β during neuroinflammation. Gene expression analysis in EAE mice showed that Sting level decreased in the peripheral lymphoid tissue, while its level increased within the central nervous system over the course of the disease. Similar patterns could be verified in peripheral immune cells during the acute phases of RRMS in comparison to remitting phases and appropriately matched healthy controls. Our study is the first to provide evidence that the STING/IFN-β-axis is downregulated in RRMS patients, meriting further intensified research to understand its role in the pathophysiology of MS and potential translational applications.

scholarly journals Innate Immune System and Multiple Sclerosis. Granulocyte Numbers Are Reduced in Patients Affected by Relapsing-Remitting Multiple Sclerosis during the Remission Phase

2020 ◽  
Vol 9 (5) ◽  
pp. 1468
Author(s):  
Zbyšek Pavelek ◽  
Francesco Angelucci ◽  
Ondřej Souček ◽  
Jan Krejsek ◽  
Lukáš Sobíšek ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Innate Immunity ◽  
Innate Immune ◽  
Healthy Controls ◽  
Statistical System ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Remission Phase ◽  
Relapsing Remitting Multiple Sclerosis

Background: Multiple sclerosis (MS) is a neurodegenerative disease that affects the central nervous system. The cause of MS is still unknown, and the role of innate immunity is still poorly understood. Objective: The goal of this study was to understand whether, compared to healthy controls, the elements of innate immunity are altered in the blood of MS patients in the remitting phase. Methods: A total of 77 naïve MS patients and 50 healthy controls were included in this cohort study. Peripheral blood samples were collected and analyzed. All the calculations were performed with the statistical system R (r-project.org). Results: The results showed that MS patients had significantly lower relative representations of granulocytes than healthy controls, while the relative representations of monocytes remained unchanged. CD64- and PD-L1-positive granulocytes exhibited a nonsignificant decreasing trend, while granulocytes with other membrane markers remained noticeably unchanged. Conclusion: The results of this study suggest that studies of the causes of MS and its treatment should also be focused on the elements of the innate immune response.

First use of alemtuzumab in Balo’s concentric sclerosis: a case report

2013 ◽  
Vol 19 (12) ◽  
pp. 1673-1675 ◽  
Author(s):  
JWL Brown ◽  
AJ Coles ◽  
JL Jones
Keyword(s):  
Multiple Sclerosis ◽  
Monoclonal Antibody ◽  
Standard Protocol ◽  
Demyelinating Disorder ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Radiological Impact ◽  
Treatment Refractory ◽  
Baló’S Concentric Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Balo’s concentric sclerosis (BCS) is a rare demyelinating disorder of the central nervous system. The humanised monoclonal antibody alemtuzumab has shown efficacy in another demyelinating disorder, relapsing–remitting multiple sclerosis. We aimed to explore its efficacy in treatment-refractory BCS. A 52-year-old male with radiologically confirmed progressive BCS resistant to steroids, plasmapharesis and cyclophosphamide was administered a standard protocol of alemtuzumab. Treatment failed to slow his decline; he died 6 months after administration. Why alemtuzumab induced no clinical or radiological impact may be multifactorial. We review the evidence directing BCS therapy and propose the next steps for exploring this potentially fatal condition.

Relapsing-Remitting Multiple Sclerosis - Current Treatment Options and Perspectives for the Future

2010 ◽  
Vol 5 (1) ◽  
pp. 78
Author(s):  
Alex Rae-Grant ◽  
Daniel Ontaneda ◽  
◽  
Keyword(s):  
Multiple Sclerosis ◽  
Treatment Options ◽  
Current Treatment ◽  
Relapsing Remitting ◽  
Significant Disability ◽  
The Central Nervous System ◽  
Disease Modifying Agents ◽  
Phase Ii And Iii ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Made In

Multiple sclerosis (MS) is the most prevalent demyelinating condition of the central nervous system and produces significant disability over time. For many years it was considered to be an untreatable disease, but great advances have been made in the treatment of MS in the last 20 years. There are currently six US Food and Drug Administration (FDA)-approved disease-modifying agents for the relapsing form of the disease. We review in detail these medications and the pivotal trials leading to their approval. We will briefly review non-FDA-approved medications already used in MS. We will also discuss some of the medications currently being studied in phase II and III trials that are not yet approved for use in MS.

Cortical plasticity predicts recovery from relapse in multiple sclerosis

2013 ◽  
Vol 20 (4) ◽  
pp. 451-457 ◽  
Author(s):  
Francesco Mori ◽  
Hajime Kusayanagi ◽  
Carolina Gabri Nicoletti ◽  
Sagit Weiss ◽  
Maria Grazia Marciani ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Synaptic Plasticity ◽  
Cortical Plasticity ◽  
Neuronal Damage ◽  
Complete Recovery ◽  
Long Term Potentiation ◽  
Term Potentiation ◽  
Relapsing Remitting ◽  
Symptom Recovery ◽  
Relapsing Remitting Multiple Sclerosis

Background: Relapsing–remitting multiple sclerosis (RRMS) is characterized by the occurrence of clinical relapses, followed by remitting phases of a neurological deficit. Clinical remission after a relapse can be complete, with a return to baseline function that was present before, but is sometimes only partial or absent. Remyelination and repair of the neuronal damage do contribute to recovery, but they are usually incomplete. Objective: We tested the hypothesis that synaptic plasticity, namely long-term potentiation (LTP), may represent an additional substrate for compensating the clinical defect that results from the incomplete repair of neuronal damage. Methods: We evaluated the correlation between a measure of LTP, named paired associative stimulation (PAS), at the time of relapse and symptom recovery, in a cohort of 22 newly-diagnosed MS patients. Results: PAS-induced LTP was normal in patients with complete recovery, and reduced in patients showing incomplete or absent recovery, 12 weeks after the relapse onset. A multivariate regression model showed that PAS-induced LTP and age may contribute to predict null, partial or complete symptom recovery after a relapse. Conclusion: Synaptic plasticity may contribute to symptom recovery after a relapse in MS; and PAS, measured during a relapse, may be used as a predictor of recovery.

A case of immune-mediated encephalitis related to daclizumab therapy

2018 ◽  
Vol 25 (5) ◽  
pp. 750-753 ◽  
Author(s):  
Michael Devlin ◽  
Andrew Swayne ◽  
Martin Newman ◽  
Cullen O’Gorman ◽  
Helen Brown ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Adverse Reactions ◽  
Brain Biopsy ◽  
Disease Modifying Therapy ◽  
Immune Mediated ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Disease Modifying ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Csf Examination

This report will detail a case of immune-mediated encephalitis in the context of daclizumab therapy. Daclizumab is a humanised monoclonal antibody which, prior to its recent worldwide withdrawal due to safety concerns, was utilised as a disease-modifying therapy in relapsing-remitting multiple sclerosis. The withdrawal of this therapy was prompted by concerns over 12 cases of serious immune-mediated adverse reactions in the central nervous system. We report an additional case, including clinical data and results of neuroimaging, cerebrospinal fluid (CSF) examination and brain biopsy.

IFN-β treatment modulates the CD28/CTLA-4-mediated pathway for IL-2 production in patients with relapsing -remitting multiple sclerosis

2004 ◽  
Vol 10 (6) ◽  
pp. 630-635 ◽  
Author(s):  
C Espejo ◽  
L Brieva ◽  
G Ruggiero ◽  
J Río ◽  
X Montalban ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Chronic Inflammatory Disease ◽  
Autoimmune Response ◽  
T Cell Proliferation ◽  
Immunomodulatory Effects ◽  
Cd25 Expression ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Relapsing Remitting Multiple Sclerosis

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system probably mediated by Th1 lymphocytes. IFN-b is an established therapy for relapsing MS patients, although the mechanisms underlying its efficacy are yet to be well characterized. We determined IL-2 production, CD25 expression and T-cell proliferation from relapsing -remitting MS patients before and three months after starting therapy. A decrease in the percentage of CD80-induced IL-2-producing cells was observed after in vivo IFN-b treatment. These data support that one of the immunomodulatory effects of IFN-b treatment in MS may be a limitation of the autoimmune response modifying the CD80:CD28/CTLA-4 pathway.

Biological markers in body fluids for activity and progression in multiple sclerosis

1999 ◽  
Vol 5 (4) ◽  
pp. 287-290
Author(s):  
Per Soelberg Sùrensen
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Biological Markers ◽  
Body Fluids ◽  
Therapeutic Effects ◽  
Therapeutic Decisions ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
The Individual ◽  
Relapsing Remitting Multiple Sclerosis

Reliable biological markers in body fluids for disease activity and progression are important for our understanding of the pathophysiology and therapeutic decisions in various subtypes of multiple sclerosis. Sampling from body fluids such as cerebrospinal fluid, blood, and urine constitutes the problem that the local immuno-inflammatory process takes place in the central nervous system whereas the disease activity is only to some extent reflected in the systemic immune compartment. Promising results have been obtained in studies of adhesion molecules, pro-inflammatory cytokines, co-stimulatory molecules and neopterin as markers of disease activity in relapsing-remitting multiple sclerosis. However, these results apply to groups of patients but not necessarily to individual patients. Currently no single body fluid marker is sufficiently correlated to disease activity to be used in the individual patient in monitoring disease activity, progression, or therapeutic effects.

scholarly journals Assessment of the influence of various risk factors on the severity of psycho-emotional disorders in patients with multiple sclerosis

2021 ◽  
Vol 17 (5) ◽  
pp. 31-35
Author(s):  
T.A. Odintsova ◽  
O.O. Kopchak
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
Emotional Disorders ◽  
Demyelinating Disease ◽  
External Factors ◽  
Depression And Anxiety ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Severity Levels ◽  
Relapsing Remitting Multiple Sclerosis

Multiple sclerosis is an insidious disabling, both physically and mentally, demyelinating disease of the central nervous system. People with multiple sclerosis, apart from the classic manifestations, can also experience depression and anxiety. The study was aimed to assess peculiarities of influence of socio-demographic, external factors, and characteristics of the disease on depression and anxiety among patients with relapsing-remitting multiple sclerosis. The following article highlights the main risk factors and their ways of influence on the aforementioned disorders, distinguished by the multifactorial analysis. Also, it estimates the frequency of different severity levels of either depression or anxiety depending on the pre-sence of each risk factor.

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