Autoimmune encephalitis: novel therapeutic targets at the preclinical level

Sell, Josefine; Haselmann, Holger; Hallermann, Stefan; Hust, Michael; Geis, Christian

doi:10.1080/14728222.2021.1856370

Cited by 18 publications

(11 citation statements)

References 99 publications

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“…Though classically attributed to infection, an autoimmune basis was reported with similar frequency for encephalitis (4). Autoimmune encephalitis (AE) is the umbrella term for autoimmune disorders in the central nervous system (CNS) characterized by the presence of autoantibodies against intracellular or membrane antigens (5). Over the past decade, the identification of an increasing number of antibodies have aided in the identification and characterization of AE (4).…”

Section: Introductionmentioning

confidence: 99%

Anti-Alpha-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid Receptor Encephalitis: A Review

et al. 2021

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Anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) encephalitis, a rare subtype of autoimmune encephalitis, was first reported by Lai et al. The AMPAR antibodies target against extracellular epitopes of the GluA1 or GluA2 subunits of the receptor. AMPARs are expressed throughout the central nervous system, especially in the hippocampus and other limbic regions. Anti-AMPAR encephalitis was more common in middle-aged women and most patients had an acute or subacute onset. Limbic encephalitis, a classic syndrome of anti-AMPAR encephalitis, was clinically characterized by a subacute disturbance of short-term memory loss, confusion, abnormal behavior and seizure. Magnetic resonance imaging often showed T2/fluid-attenuated inversion-recovery hyperintensities in the bilateral medial temporal lobe. For suspected patients, paired serum and cerebrospinal fluid (CSF) testing with cell-based assay were recommended. CSF specimen was preferred given its higher sensitivity. Most patients with anti-AMPAR encephalitis were complicated with tumors, such as thymoma, small cell lung cancer, breast cancer, and ovarian cancer. First-line treatments included high-dose steroids, intravenous immunoglobulin and plasma exchange. Second-line treatments, including rituximab and cyclophosphamide, can be initiated in patients who were non-reactive to first-line treatment. Most patients with anti-AMPAR encephalitis showed a partial neurologic response to immunotherapy.

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Section: Introductionmentioning

confidence: 99%

Anti-Alpha-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid Receptor Encephalitis: A Review

et al. 2021

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“…After these therapies, up to 75–80% of patients achieve good outcomes and reassume their daily activities. However, refractory patients may benefit from alternative drugs, such as tocilizumab, bortezomib, or daratumumab, which could be considered based on the effectiveness reported in small case series [ 37 , 38 , 39 , 40 , 41 ].…”

Section: An Overview Of Anti-nmdar Encephalitismentioning

confidence: 99%

Current Status of Biomarkers in Anti-N-Methyl-D-Aspartate Receptor Encephalitis

Ciano-Petersen

Cabezudo‐García

Muñiz‐Castrillo

et al. 2021

IJMS

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The discovery of biomarkers in rare diseases is of paramount importance to allow a better diagnosis, improve predictions of outcomes, and prompt the development of new treatments. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a rare autoimmune disorder associated with the presence of antibodies targeting the GluN1 subunit of the NMDAR. Since it was discovered in 2007, large efforts have been made towards the identification of clinical, paraclinical, and molecular biomarkers to better understand the immune mechanisms that govern the course of the disease as well as to define predictors of treatment response and long-term outcomes. However, most of these biomarkers are still in an exploratory phase, with only a few candidates reaching the final phases of the always-complex process of biomarker development, mainly due to the low incidence of the disease and its recent description. Clinical and paraclinical markers are probably the most widely explored in anti-NMDAR encephalitis, five of them combined in a clinical score to predict 1 year outcome. On the contrary, soluble molecules, such as persistent antibody positivity, antibody titers, cytokines, and other inflammatory mediators, have been proposed as biomarkers of clinical activity, inflammation, prognosis, and treatment response, but further studies are required for their clinical validation including larger and more homogenous cohorts of patients. Similarly, genetic susceptibility biomarkers are still in the exploratory phase and, therefore, weak conclusions can for now only be achieved. Thus, further studies are warranted to define biomarkers and unravel the underlying mechanisms driving rare diseases such as anti-NMDAR encephalitis. Future international collaborative studies with prospective designs that enable the enrollment of large cohorts will allow for the identification and validation of novel biomarkers for clinical decision-making.

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“…Although only one randomized, placebo-controlled trial from Dubey et al (4) exists for immunotherapy in autoimmune encephalitis, many observational and case series have been published on it. There is consensus among experts concerning first-line therapy encompassing methylpredisolone and/or IVIG (intravenous immunoglobulins) and/or plasmapheresis (PLEX)/immunadsorption (2,(5)(6)(7). Second-line immunotherapy consists of rituximab or cyclophosphamide (2,(5)(6)(7).…”

Section: Lessons From Immunotherapy In Autoimmune Encephalitismentioning

confidence: 99%

“…There is consensus among experts concerning first-line therapy encompassing methylpredisolone and/or IVIG (intravenous immunoglobulins) and/or plasmapheresis (PLEX)/immunadsorption (2,(5)(6)(7). Second-line immunotherapy consists of rituximab or cyclophosphamide (2,(5)(6)(7). If methylprednisolone proves effective in first-line therapy, steroid-saving drugs such as mycophenolate or azathioprine might be used for maintenance therapy (5-7).…”

Section: Lessons From Immunotherapy In Autoimmune Encephalitismentioning

confidence: 99%

Immunotherapy in Autoantibody-Associated Psychiatric Syndromes in Adults

Hansen

Timäus

2021

Front. Psychiatry

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Background: Autoantibody-associated psychiatric syndromes are often distinct from, but might also be part of autoimmune encephalitis. Our article focuses on potential immunotherapy in these patients with a probable autoimmune origin of their psychiatric syndrome.Methods: We searched through PubMed for appropriate articles on immunotherapy in autoantibody-associated psychiatric syndromes between 2010 and 2020 for this narrative review.Results: In line with prior recommendations for autoimmune encephalitis and autoimmune psychosis, we suggest that in patients with a probable autoimmune-based psychiatric syndrome should be given early corticosteroids, intravenous immunoglobulins, or plasmapheresis as first line immunotherapy. If these therapeutic options fail, second-line immunotherapy should be applied within 1 month consisting of rituximab or cyclophosphamide. Maintenance therapy is best for those patients responding to steroids including mycofenolate mofetil or azathioprine. So far, there is evidence from a few retrospective cohort studies supporting the usage of first- and second-line, and maintenance immunotherapies for autoantibody-associated psychiatric syndromes. Some immunological agents are discussed that might exert an effect in autoimmune-based psychiatric syndromes, but the latest evidence is low and derived from case reports or series with autoimmune encephalitis patients.Conclusions: Taken together, the immunotherapeutic landscape for patients with autoantibody-associated psychiatric syndromes is delineated. Our suggestions rely on observational studies in autoantibody-associated psychiatric syndromes and a few placebo-controlled, randomized trials for patients with autoimmune encephalitis and psychosis. Thus, adequate powered, prospective as well as placebo-controlled clinical trials in patients with autoantibody-associated psychiatric syndromes are warranted in order to enlighten efficacy and safety aspects of current and novel therapy strategies.

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Autoimmune encephalitis: novel therapeutic targets at the preclinical level

Cited by 18 publications

References 99 publications

Anti-Alpha-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid Receptor Encephalitis: A Review

Anti-Alpha-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid Receptor Encephalitis: A Review

Current Status of Biomarkers in Anti-N-Methyl-D-Aspartate Receptor Encephalitis

Immunotherapy in Autoantibody-Associated Psychiatric Syndromes in Adults

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