An uncontrolled trial of rituximab for antibody associated paraneoplastic neurological syndromes

Shamsili, Setareh; Beukelaar, Janet de; Gratama, Jan W.; Hooijkaas, Herbert; Bent, Martin J. van den; Veer, Mars van 't; Smitt, Peter Sillevis

doi:10.1007/s00415-005-0882-0

Cited by 169 publications

(86 citation statements)

References 22 publications

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“…Rituximab (anti-CD20) was administered to 9 patients with newly diagnosed anti-Hu-or anti-Yo-associated PND at a dose of 375 mg/m 2 for up to 4 infusions [79]. In 3/9 patients, symptoms improved by a >1 point decrease in the Rankin Scale.…”

Section: Targeted Therapy For Pndmentioning

confidence: 99%

Neuroinflammation: Ways in Which the Immune System Affects the Brain

et al. 2015

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Neuroinflammation is the response of the central nervous system (CNS) to disturbed homeostasis and typifies all neurological diseases. The main reactive components of the CNS include microglial cells and infiltrating myeloid cells, astrocytes, oligodendrocytes, and the blood-brain b a r r i e r , c y t o k i n e s , a n d c y t o k i n e s i g n a l i n g . Neuroinflammatory responses may be helpful or harmful, as mechanisms associated with neuroinflammation are involved in normal brain development, as well as in neuropathological processes. This review examines the roles of various cell types that contribute to the immune dysregulation associated with neuroinflammation. Microglia enter the CNS very early in embryonic development and, as such, play an essential role in both the healthy and diseased brain. B-cell diversity contributes to CNS disease through both antibody-dependent and antibody-independent mechanisms. The influences of these B-cell mechanisms on other cell types, including myeloid cells and T cells, are reviewed in relationship to antibody-mediated CNS disorders, paraneoplastic neurological diseases, and multiple sclerosis. New insights into neuroinflammation offer exciting opportunities to investigate potential therapeutic targets for debilitating CNS diseases.

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Section: Targeted Therapy For Pndmentioning

confidence: 99%

Neuroinflammation: Ways in Which the Immune System Affects the Brain

et al. 2015

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“…Incidental improvement has been reported either spontaneously or in association with plasma exchange, steroids, i.v. Ig, or rituximab [52]. In patients with anti-Yoassociated cerebellar degeneration, the prognosis is better for patients with breast cancer than for those with gynecologic cancer [5].…”

Section: Treatment and Prognosismentioning

confidence: 99%

Managing Paraneoplastic Neurological Disorders

2006

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“…Basically, IVIG treatment and apheresis therapies are more effective in patients with Abs directed against surface antigens compared to in-tracellular antigens with mainly T cell-mediated immune responses [3,16,19,20]. If the patient does no improve with acute treatment, an early (typically up to 2 weeks after the above-mentioned primary treatment) escalation to cyclophosphamide (as a shortterm high-dose treatment with 750-1000 mg/m 2 IV) or rituximab (e. g., 500 mg IV on days 1 and 15) can be undertaken [16,21,22]. Here, it is important to ensure that the patient receives appropriate concomitant medications, such as uromitexan along with cyclophosphamide or steroids and antihistamines along with rituximab.…”

Section: Principles Of Immunotherapymentioning

confidence: 99%

Management of Immune-Mediated Paraneoplastic Neurological Disorders

Ayzenberg

Gold

Kleiter

2017

Neurology International Open

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AbsTR Ac TParaneoplastic neurological disorders are rare and clinically heterogeneous diseases. They can affect both the central and peripheral nervous system as well as the neuromuscular junction and muscle. Neurological deficits develop in 2/3 of cases prior to cancer diagnosis. The diagnostic approach includes screening for antineuronal antibodies and a search for the underlying tumor. A prompt tumor therapy in combination with immunotherapy is the cornerstone in the management of these diseases. Due to lack of clinical trials, treatment recommendations are based on case series and expert opinions. Highdose corticosteroids, intravenous immunoglobulins and apheresis therapies are often used in the acute stage of the disease. These therapies should be started as early as possible, e. g., during tumor screening, in order to prevent irreversible damage. Long-term treatment is mostly immunosuppressive and depends on the specific paraneoplastic syndrome. Outcomes vary depending upon the prognosis of the underlying cancer and the nature of the antineuronal antibodies. Disorders with antibodies directed against antigens on the neuronal cell surface are highly sensitive to B cell-directed therapies and mostly associated with a favorable outcome. A thorough review of published data on actual treatment recommendation is provided along with discussion of currently not validated, but potentially effective new therapies. E264Ayzenberg I et al. Management of Immune-mediated Paraneoplastic … Neurology International Open 2017; 1: E264-E274 course, treatment response and prognosis of PNS [2,3]. Depending on tumor association, obligate and facultative paraneoplastic Abs are differentiated (Tab. 1).Clinically, the following PNS exist [3,4]: A. In the central nervous system: ▪ Encephalomyelitis (incl. brainstem encephalitis) ▪ Limbic encephalitis ▪ Subacute cerebellar degeneration ▪ Opsoclonus-myoclonus syndrome ▪ Optic neuritis/neuromyelitis optica ▪ Myelopathy/myelitis ▪ Stiff person syndrome ▶Table 1 Paraneoplastic antibodies: associated neurological syndromes and tumors. Target antigen clinical presentation# Association with tumorObligate paraneoplastic Abs (directed against intracellular antigens; tumor association > 95 %) In this review we discuss the diagnosis and management of PNS. With regard to facultative paraneoplastic syndromes which are more frequently of autoimmune origin, such as neuromyelitis optica or myasthenia gravis, the reader should refer to pertinent reviews [5,6]. Diagnostic and Pathogenetic Significance of Antibodies to Intracellular and Surface AntigensAntibodies (Abs) to intracellular antigens or so-called "classical" Abs are almost always tumor-associated (exception: GAD-Abs). They can be associated with various tumors and a variety of neurological conditions [7]. However, a direct pathogenetic significance of these Abs has not yet been demonstrated. Abs to intracellular antigens serve as useful diagnostic markers in the targeted tumor search in PNS. Here, cell-mediated immune responses play a major p...

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An uncontrolled trial of rituximab for antibody associated paraneoplastic neurological syndromes

Cited by 169 publications

References 22 publications

Neuroinflammation: Ways in Which the Immune System Affects the Brain

Neuroinflammation: Ways in Which the Immune System Affects the Brain

Managing Paraneoplastic Neurological Disorders

Management of Immune-Mediated Paraneoplastic Neurological Disorders

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