401 General Military Hospital of Athens
Neurology

Author Of 2 Presentations

Disease Modifying Therapies – Risk Management Poster Presentation

P0352 - Lymphocyte Subtypes Repopulation Pattern and Secondary Autoimmunity in patients with RRMS treated with Alemtuzumab in a Real World setting (ID 1112)

Speakers
Presentation Number
P0352
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

Alemtuzumab is a humanized monoclonal antibody targeting CD52 expressing T and B lymphocytes used as a second line treatment for patients with highly active Relapsing Remitting Multiple Sclerosis (RRMS). Treatment with alemtuzumab has been associated with increased incidence of secondary auto-immune adverse events. Although the exact underlying mechanisms remain unclear, it has been hypothesized that secondary auto-immunity is a result of the fast / excessive repopulation of autoreactive CD19 lymphocytes following their initial depletion.

Objectives

To investigate the potential association of peripheral lymphocyte subtypes kinetics following treatment with Αlemtuzumab with auto-immune adverse events as well as with disease activity and disease progression in patients with RRMS, in a real-world setting.

Methods

Α retrospective analysis of data from a series of 33 patients that received two courses of treatment and completed at least 24 months of follow up was performed. Primary endpoints included incidence of new or exacerbation of preexisting auto-immunities, disease activity and disease progression in association with lymphocyte depletion and repopulation patterns. Lymphocyte subpopulations (CD4+/CD8+ T cells, CD19+ B cells total and memory, CD56 NK cells) were measured using flow cytometry at baseline and at months one, three, six and twelve after each treatment course. Patients were assessed clinically and with MRI every six months throughout the 2-year follow-up period. Statistical analysis included generalized linear models for repeated measures.

Results

Overall, 17 adverse events of autoimmune origin and 2 cases of exacerbation of previously existing auto-immunities were observed. Lymphocyte repopulation patterns did not show significant differences in association with incidence of auto-immune reactions. Repopulation kinetics were also unrelated to any other primary outcome investigated in this study.

Conclusions

Our findings suggest that lymphocytes repopulation patterns do not have a predictive value of the incidence of secondary auto-immunity, as well as the activity and the progression of the disease, following treatment with Alemtuzumab. The mechanisms behind the differentiation among patients in regards to autoimmune reactions may lie in more specific lymphocyte subpopulations that have not been included in this study or in deeper molecular paths mediated by specific cytokines. Further study is required in this field.

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Neuromyelitis Optica and Anti-MOG Disease Poster Presentation

P0733 - Neuromyelitis Optica Spectrum Disorder with Interstitial Pneumonia as the First Episode: A Case Report (ID 1124)

Speakers
Presentation Number
P0733
Presentation Topic
Neuromyelitis Optica and Anti-MOG Disease

Abstract

Background

Neuromyelitis Optica Spectrum Disorder (NMOSD) describes a range of immune-mediated inflammatory conditions typically presenting as recurrent episodes of optic neuritis and myelitis. The main pathogenic factor is the presence of immunoglobulin (Ig)G antibodies against the water channel protein aquaporin4 (AQP4) in the blood and subsequently in the central nervous system (CNS). Although, initially, it was considered that AQP4-IgG particularly targets the CNS, recently few cases with concurrent manifestations from other peripheral organs have been reported.

Objectives

Herein, we describe a rare case of NMO with atypical first manifestation of pneumonia and multisystem involvement including skeletal muscles, blood system and kidneys, additionally to the CNS.

Methods

A 77-year-old female was initially admitted to the pulmonology department where she was investigated for interstitial pneumonia. The patient underwent computed tomography that revealed abnormal shadows distributed in both lungs. Bronchoscopy and lung biopsies were non-diagnostic. During hospitalization she experienced a sudden onset of hiccups and vomiting. Simultaneously, numbness and muscle weakness of lower extremities were established. Magnetic resonance imaging (MRI) showed high-intensity signals at area postrema region and intramedullary at cervical and thoracic spinal cord on T2-weighted imaging, with gadolinium enhancement on T1-weighted imaging. Cerebrospinal fluid (CSF) examination revealed mild lymphocytosis, oligoclonal bands identical in CSF and serum, compatible with systematic inflammatory disease and positive AQP4-IgG antibodies. Based on the above findings the diagnosis of NMOSD was established. In the following days myalgia with high levels of creatine phosphokinase were noticed. Furthermore, acute renal failure and severe anemia occurred. A full panel of tests for autoimmune, viral and paraneoplastic disorders was carried out to exclude other pathological conditions. Positron emission tomography (PET) scan was without pathological findings.

Results

The patient received high doses of intravenous corticosteroids followed by oral prednisolone in long term with gradual improvement of her symptoms both on the CNS and the periphery.

Conclusions

This case highlights the possible involvement of tissues other than the CNS in AQP4-IgG positive patients. Clinicians should be aware of atypical manifestations of NMOSD outside the CNS, in cases where examinations are non-diagnostic and any other autoimmune or paraneoplastic disorder is excluded.

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