Rituximab (anti-CD20) Adjunctive Therapy for Opsoclonus-Myoclonus Syndrome

Pranzatelli, Michael R.; Tate, Elizabeth D.; Travelstead, Anna L.; Barbosa, Jerry L.; Bergamini, Robert A.; Civitello, Lucy; Franz, David Neal; Greffe, Brian; Hanson, Robin; Hurwitz, Craig A.; Kalinyak, Karen; Kelfer, Howard; Khakoo, Yasmin; Mantovani, John F.; Nicholson, Stacy; Sanders, J.; Wegner, Stephen

doi:10.1097/01.mph.0000212991.64435.f0

Cited by 128 publications

(72 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In both patients there was very significant B-cell expansion, similar to or higher than that described in cases of opsoclonusmyoclonus syndrome, a putative autoimmune disorder that can be treated with rituximab. 7 This finding supports the role of CSF humoral autoimmunity in both the acute and relapsing course of NMDAR encephalitis. Given the fact that many patients with NMDAR encephalitis exhibit intrathecal synthesis of NMDAR antibody, B-cell expansion and differentiation would be anticipated and expected.…”

Section: Discussionsupporting

confidence: 75%

“…6,7 We present our findings of CSF B-cell expansion in a child with acute NMDAR encephalitis and in another child with relapsing NMDAR encephalitis. Both children had substantial expansion of B-cells in the CSF, a finding that supports the use of drugs such as rituximab that target CD20 + B-cells.…”

mentioning

confidence: 98%

“…5 CSF immunophenotyping has demonstrated B-cell expansion in opsoclonus-myoclonus and neuromyelitis optica, and has been used to support the humoral autoimmune hypothesis, and the use of drugs that deplete B-cell populations such as rituximab. 6,7 We present our findings of CSF B-cell expansion in a child with acute NMDAR encephalitis and in another child with relapsing NMDAR encephalitis. Both children had substantial expansion of B-cells in the CSF, a finding that supports the use of drugs such as rituximab that target CD20 + B-cells.…”

mentioning

confidence: 98%

See 2 more Smart Citations

Cerebrospinal fluid CD19⁺ B‐cell expansion in N‐methyl‐D‐aspartate receptor encephalitis

Dale

Pillai

Brilot

2012

Develop Med Child Neuro

View full text Add to dashboard Cite

ABBREVIATIONS CSFCerebrospinal fluid NMDAR N-methyl-D-aspartate receptorThere is increasing interest in the role of autoantibodies in acquired autoimmune central nervous system disorders. N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune encephalitis defined by the presence of autoantibodies that bind to the NMDAR. Although there is evidence of NMDAR antibody pathogenicity, it is unclear which treatment results in the best outcome. We measured the proportion of B-cells in the cerebrospinal fluid of two children with NMDAR encephalitis (a 6-year-old male and a 4-year-old female), one in the acute phase and one in the relapsing phase. The proportion of CD19 + B-cells in both children was greater than 10%, significantly higher than seen in non-inflammatory neurological disorders (<1%). This finding supports the use of drugs, such as rituximab, that deplete B-cells in severe or refractory cases of NMDAR encephalitis, and lends further support to the humoral autoimmune hypothesis in NMDAR encephalitis.There is increasing interest in the role of central nervous system autoimmunity mediated by B-cells and autoantibodies.Antibodies that bind to neuronal receptors and synaptic proteins are increasingly important biomarkers and mediators of acquired neurological and psychiatric disease. 1,2N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune encephalitis that affects children and young adults, and is defined by serum and cerebrospinal fluid (CSF) autoantibodies against the NR1 subunit of the NMDAR. There is already clear evidence that NMDAR antibodies have a pathogenic role and down-regulate the receptor from the neuronal cell surface. 1,3 Some pathological studies have shown that the parenchymal inflammatory infiltrate in perivascular regions has an excess of plasmablasts and CD138 plasma cells, 4 although a separate report has shown a low density of inflammatory cells and very limited neuropathology. 5CSF immunophenotyping has demonstrated B-cell expansion in opsoclonus-myoclonus and neuromyelitis optica, and has been used to support the humoral autoimmune hypothesis, and the use of drugs that deplete B-cell populations such as rituximab. 6,7 We present our findings of CSF B-cell expansion in a child with acute NMDAR encephalitis and in another child with relapsing NMDAR encephalitis. Both children had substantial expansion of B-cells in the CSF, a finding that supports the use of drugs such as rituximab that target CD20 + B-cells. CASE REPORTS MethodLymphocyte immunophenotyping was performed using a previously described protocol. 6 CSF samples (range 10-500lL with a red blood cell count <100 red blood cells per mm 3 ) were collected and immediately placed on ice, and then centrifuged at 600g for 7 minutes at 4°C. It was usually possible to perform CSF immunophenotyping with less than 1mL of CSF. Non-specific Fc receptor binding was blocked with 0.2mg ⁄ mL normal mouse immunoglobulin G (Invitrogen, Carlsbad, CA, USA) for 15 minutes at room temperature. Directly labelled anti-CD3 (clone U...

show abstract

Section: Discussionsupporting

confidence: 75%

mentioning

confidence: 98%

mentioning

confidence: 98%

See 1 more Smart Citation

Cerebrospinal fluid CD19⁺ B‐cell expansion in N‐methyl‐D‐aspartate receptor encephalitis

Dale

Pillai

Brilot

2012

Develop Med Child Neuro

View full text Add to dashboard Cite

show abstract

“…Thus, our experimental results supported the immunological evidence that this patient's serum sample includes an antibody with affinity to NMDAR. Rituximab causes a decrease in B cells and prevents maturation of these cells into antibody-secreting cells (10); it also suppresses B cell function more selectively and continuously than first-line immunotherapy (13)(14)(15)(16)(17)(18)(19). In addition, this agent causes a form of immune system resetting due to the depletion of memory B cells (19,20).…”

Section: Discussionmentioning

confidence: 99%

Rituximab Used Successfully in the Treatment of Anti-NMDA Receptor Encephalitis

et al. 2012

View full text Add to dashboard Cite

We report the case of a young woman with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, without tumor, who was successfully treated with rituximab. Because conventional immunotherapy, including corticosteroids, immunoglobulin (IVIg), and plasma exchange showed little improvement in our patient, we introduced another treatment using rituximab. A week after the first administration of rituximab, her symptoms improved gradually and significantly. This case provides in vivo evidence that rituximab is an effective agent for treating anti-NMDAR encephalitis, even in those cases where conventional immunotherapies have been ineffective. Rituximab should be regarded as a beneficial therapeutic agent for this disease.

show abstract

“…Treatment possibility is less in children when compared to adults (Bataller et al, 2001). Rituximab therapy may be tried in suitable patients (Pranzatelli et al, 2006).…”

Section: Opsoclonus-myoclonusmentioning

confidence: 99%

Paraneoplastic neurologic disorders

Şen¹,

Terzı²

2013

jecm

View full text Add to dashboard Cite

IntroductionParaneoplastic neurologic syndromes (PNS) are manifestations of cancers which are located outside the central nervous system. They appear before the diagnosis of cancer in most of patients. Identification of these disorders is very important as it leads to diagnosis and treatment of cancer subsequently. PNS are divided into two groups as classical and non-classical. Classical PNS are associated with cancer more than non-classical PNS. Non-classical PNS are rather observed in cases without cancer. PNS can also be divided into two groups as per the involvement of the central and peripheral nervous system (Table 1) (Bradley, 2008;Tüzün, 2010). EpidemiologyPNS are rare disorders in cancer patients. Frequency in all cancer patients is 0.01% (Darnell and Posner, 2003). Women/ men ratio is approximately 3:1. It is usually observed beyond mid-life. They show a closer association with some kinds of cancer. They have a more frequent association especially with hematologic diseases such as small cell lung cancer (SCLC), thymoma, and monoclonal gammopathy. Other can-cer types associated with PNS include breast, gynecological cancers such as ovarian and Hodgkin's, non-Hodgkin's lymphoma, testicular cancer and neuroblastoma (Toothaker and Rubin, 2009). Furthermore, development of PNS is possible in almost all neoplasms (Bataller and Dalmau, 2003). PathogenesisA widely accepted opinion is that these disorders occur due to stimulation of immune response by some proteins which are formed by a tumor, against both the tumor and the nervous system (Tüzün, 2010). Cytotoxic T-cell responses have a very important role in pathogenesis of PNS (Bradley, 2008). T-cells are responsible for both of the antibody-mediated processes (Albert et al., 1998). Lymphocytic pleocytosis and oligoclonal band positivity may be observed in BOS analysis (Armstrong et al., 2005).PNS are formed by antibodies developed against the intracellular antigen or neuronal surface antigen. In limbic encephalitis, there are antibodies for both regions. Anti Hu, anti Yo, anti Ri, anti Ma2, Cv2/CRMP5 are antibodies associated with intracellular antigen, whereas the VGKC complex

show abstract

Rituximab (anti-CD20) Adjunctive Therapy for Opsoclonus-Myoclonus Syndrome

Abstract: Rituximab seems efficacious and safe as adjunctive therapy for OMS. Selective targeting of CSF B lymphocytes represents a novel and valuable paradigm shift in the therapy for centrally mediated paraneoplastic disorders.

Cited by 128 publications

References 47 publications

Cerebrospinal fluid CD19⁺ B‐cell expansion in N‐methyl‐D‐aspartate receptor encephalitis

Cerebrospinal fluid CD19⁺ B‐cell expansion in N‐methyl‐D‐aspartate receptor encephalitis

Rituximab Used Successfully in the Treatment of Anti-NMDA Receptor Encephalitis

Paraneoplastic neurologic disorders

Contact Info

Product

Resources

About

Rituximab (anti-CD20) Adjunctive Therapy for Opsoclonus-Myoclonus Syndrome

Abstract: Rituximab seems efficacious and safe as adjunctive therapy for OMS. Selective targeting of CSF B lymphocytes represents a novel and valuable paradigm shift in the therapy for centrally mediated paraneoplastic disorders.

Cited by 128 publications

References 47 publications

Cerebrospinal fluid CD19+ B‐cell expansion in N‐methyl‐D‐aspartate receptor encephalitis

Cerebrospinal fluid CD19+ B‐cell expansion in N‐methyl‐D‐aspartate receptor encephalitis

Rituximab Used Successfully in the Treatment of Anti-NMDA Receptor Encephalitis

Paraneoplastic neurologic disorders

Contact Info

Product

Resources

About

Cerebrospinal fluid CD19⁺ B‐cell expansion in N‐methyl‐D‐aspartate receptor encephalitis

Cerebrospinal fluid CD19⁺ B‐cell expansion in N‐methyl‐D‐aspartate receptor encephalitis