Anti–<i>N-</i>Methyl-<scp>d</scp>-Aspartate Receptor Encephalitis

Thomas, Alissa A.; Rauschkolb, Paula; Gresa-Arribas, Núria; Schned, Alan R.; Dalmau, Josep; Fadul, Camilo E.

doi:10.1001/jamaneurol.2013.3205

Cited by 16 publications

(6 citation statements)

References 9 publications

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“…Regarding second-line immunotherapies, this evidence synthesis showed a striking association of rituximab administration with monophasic course, with 5.9-fold reduced odds of relapse after 24 months or more follow-up, also confirmed across all the major age groups in univariate analyses (eTable 9 in the Supplement). Our review also showed the emerging use of escalation second-line therapies, such as intravenous/intrathecal methotrexate, subcutaneous/intravenous bortezomib, and intravenous tocilizumab, in a very limited subset of patients (eTable 4 in the Supplement), insufficient for inclusion in our multivariable modeling . Their efficacy and safety in NMDARE warrant further investigation .…”

Section: Discussionmentioning

confidence: 86%

Use and Safety of Immunotherapeutic Management of N-Methyl-d-Aspartate Receptor Antibody Encephalitis

et al. 2021

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Key Points Question What are the most effective treatments for N -methyl- d -aspartate receptor (NMDAR) antibody encephalitis? Findings In this meta-analysis of individual patient data including 1550 cases, treatment factors at first event that were significantly associated with good functional outcome 12 months from disease onset included first-line treatment with therapeutic apheresis alone, corticosteroids in combination with intravenous immunoglobulin (IVIG), or corticosteroids in combination with IVIG and therapeutic apheresis, while lack of immunotherapy within 30 days of disease onset was significantly associated with poor outcome. Rituximab and long-term IVIG use were significantly associated with nonrelapsing disease course. Meaning Separate treatment factors are associated with functional outcomes and relapsing disease biology in those with NMDAR antibody encephalitis.

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Section: Discussionmentioning

confidence: 86%

Use and Safety of Immunotherapeutic Management of N-Methyl-d-Aspartate Receptor Antibody Encephalitis

et al. 2021

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“…42-44 Other escalation treatments have been reported in the literature, such as IV/intrathecal methotrexate with intrathecal corticosteroids and subcutaneous/IV bortezomib; these have more limited evidence, but can be used according to the local treating center's expertise. 41,43-57…”

Section: Discussionmentioning

confidence: 99%

“…[42][43][44] Other escalation treatments have been reported in the literature, such as IV/intrathecal methotrexate with intrathecal corticosteroids and subcutaneous/IV bortezomib; these have more limited evidence, but can be used according to the local treating center's expertise. 41,[43][44][45][46][47][48][49][50][51][52][53][54][55][56][57] The patient who has severe disease and is failing to improve remains a major challenge. The clinician needs to balance the risk of severe disease (such as being on the intensive care unit) with the risk of treatment side effects, in the knowledge that NMDARE symptoms may take many weeks or months to improve.…”

Section: Tocilizumabmentioning

confidence: 99%

International Consensus Recommendations for the Treatment of Pediatric NMDAR Antibody Encephalitis

Nosadini

Thomas

Eyre

et al. 2021

Neurol Neuroimmunol Neuroinflamm

112

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ObjectiveTo create an international consensus treatment recommendation for pediatric NMDA receptor antibody encephalitis (NMDARE).MethodsAfter selection of a panel of 27 experts with representation from all continents, a 2-step Delphi method was adopted to develop consensus on relevant treatment regimens and statements, along with key definitions in pediatric NMDARE (disease severity, failure to improve, and relapse). Finally, an online face-to-face meeting was held to reach consensus (defined as ≥75% agreement).ResultsCorticosteroids are recommended in all children with NMDARE (pulsed IV preferred), with additional IV immunoglobulin or plasma exchange in severe patients. Prolonged first-line immunotherapy can be offered for up to 3–12 months (oral corticosteroids or monthly IV corticosteroids/immunoglobulin), dependent on disease severity. Second-line treatments are recommended for cases refractory to first-line therapies (rituximab preferred over cyclophosphamide) and should be considered about 2 weeks after first-line initiation. Further immunotherapies for refractory disease 1-3 months after second-line initiation include another second-line treatment (such as cyclophosphamide) and escalation to tocilizumab. Maintenance immune suppression beyond 6 months (such as rituximab redosing or mycophenolate mofetil) is generally not required, except for patients with a more severe course or prolonged impairments and hospitalization. For patients with relapsing disease, second-line and prolonged maintenance therapy should be considered. The treatment of NMDARE following herpes simplex encephalitis should be similar to idiopathic NMDARE. Broad guidance is provided for the total treatment duration (first line, second line, and maintenance), which is dictated by the severity and clinical course (i.e., median 3, 9 and 18 months in the best, average, and worst responders, respectively). Recommendations on the timing of oncologic searches are provided.ConclusionThese international consensus recommendations for the management of pediatric NMDARE aim to standardize the treatment and provide practical guidance for clinicians, rather than absolute rules. A similar recommendation could be applicable to adult patients.

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“…Case reports occasionally describe reduction [ 6 , 22 , 26 , 32 ] or eradication [ 33 , 34 ] of NMDAR Abs in serum following first-line immunotherapy in patients with good outcome, with concomitant decrease in CSF titers [ 6 , 22 , 26 , 32 – 34 ]. Reductions in CSF titers with second-line treatments have also been demonstrated [ 31 , 35 , 36 ], but for obvious practical reasons CSF titers are not widely available in patients who have improved. Successful aggressive immunosuppression with intrathecal MTX and intravenous (IV) alemtuzumab was reported in 4 children [ 37 , 38 ], 2 of whom were refractory to prolonged immunotherapy, including cyclophosphamide and/or rituximab.…”

Section: N -Methyl D-aspartate Receptormentioning

confidence: 99%

Antibody-Mediated Autoimmune Encephalopathies and Immunotherapies

2016

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Over the last 15 years it has become clear that rare but highly recognizable diseases of the central nervous system (CNS), including newly identified forms of limbic encephalitis and other encephalopathies, are likely to be mediated by antibodies (Abs) to CNS proteins. The Abs are directed against membrane receptors and ion channel-associated proteins that are expressed on the surface of neurons in the CNS, such as N-methyl D-aspartate receptors and leucine-rich, glioma inactivated 1 protein and contactin-associated protein like 2, that are associated with voltage-gated potassium channels. The diseases are not invariably cancer-related and are therefore different from the classical paraneoplastic neurological diseases that are associated with, but not caused by, Abs to intracellular proteins. Most importantly, the new antibody-associated diseases almost invariably respond to immunotherapies with considerable and sometimes complete recovery, and there is convincing evidence of their pathogenicity in the relatively limited studies performed so far. Treatments include first-line steroids, intravenous immunoglobulins, and plasma exchange, and second-line rituximab and cyclophosphamide, followed in many cases by steroid-sparing agents in the long-term. This review focuses mainly on N-methyl D-aspartate receptor- and voltage-gated potassium channel complex-related Abs in adults, the clinical phenotypes, and treatment responses. Pediatric cases are referred to but not reviewed in detail. As there have been very few prospective studies, the conclusions regarding immunotherapies are based on retrospective studies.Electronic supplementary materialThe online version of this article (doi:10.1007/s13311-015-0410-6) contains supplementary material, which is available to authorized users.

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Anti–N-Methyl-d-Aspartate Receptor Encephalitis

Cited by 16 publications

References 9 publications

Use and Safety of Immunotherapeutic Management of N-Methyl-d-Aspartate Receptor Antibody Encephalitis

Use and Safety of Immunotherapeutic Management of N-Methyl-d-Aspartate Receptor Antibody Encephalitis

International Consensus Recommendations for the Treatment of Pediatric NMDAR Antibody Encephalitis

Antibody-Mediated Autoimmune Encephalopathies and Immunotherapies

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