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Immunotherapy in autoantibody-associated psychiatric syndromes in adults

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Encephalitis is an infectious inflammation emerging within the brain that often affects the temporal lobe and requires urgent action to prevent further brain damage. However, encephalitis can be characterized as infectious encephalitis, however it can also have an autoimmune-origin, as in autoimmune encephalitis. Autoimmune encephalitis is a disease characterized by seizures, memory disturbances, or psychiatric features in addition to changes in mesiotemporal or extratemporal brain structures in magnetic resonance imaging (MRI), pleocytosis in cerebrospinal fluid (CSF), focal epileptic potentials or slowing in temporal or extratemporal electroencephalography (EEG) ( 1 , 2 ). We need to distinguish between autoantibody-positive and negative autoimmune encephalitis, and isolated or partly isolated psychiatric symptoms revealing additional hints for an underlying immunopathology. The differentiation between autoimmune encephalitis and autoantibody-based psychiatric syndromes are not clear and might overlapping. If a psychiatric syndrome is detected and autoimmune encephalitis is diagnosed, this disease entity should be called autoimmune encephalitis as the cause is an encephalitis in its nature, although its presentation may be purely psychiatric. However, if a psychiatric syndrome dominates and no specific criteria of possible or probable autoimmune encephalitis are fulfilled, then any psychiatric syndrome’s autoimmune basis must be subjected to further investigations, such as a recent diagnostic approach ( 3 ) that has relevance for the later application of immunotherapy. We recently developed criteria ( 3 ) by which such a psychiatric syndrome can be classified as having an probable or definitive autoimmune basis. A probable autoimmune origin can be assumed if patients present with a subacute (≤ 3 months) or chronic (≥ 3 months) psychiatric syndrome affecting different symptom clusters such as altered consciousness, disorientation, confusion, memory impairment, obsessive-compulsive behavior, psychosis, catatonia, mood dysfunction, anxiety, behavioral abnormalities (autism, hyperkinetic) and/or sleeping dysfunction. In addition, ≥ 1/9 cardinal features should coincide in these patients, namely the actual or recent diagnosis of a tumor, movement disorder (catatonia, hypo- or hyperkinetic movements), adverse response to antipsychotics or antidepressants, differentially suspected neuroleptic malignant syndrome, severe cognitive dysfunction, altered consciousness, seizures, optic hallucinations, infectious prodrome with fever, aphasia, dysarthria and/or mutism. Furthermore, one of the following criteria must be met: (i) CSF pleoycytosis of > 5 μl white blood cells per μL, oligoclonal bands or intrathecal immunoglobulin G (IgG) synthesis in the CSF, (ii) uni- or bilateral brain abnormalities/ unilateral brain abnormalities on MRI within the temporal lobe or hyperintense lesions outside the limbic system, (iii) EEG abnormalities [spike, spike wave, focal slowing, extreme delta brush, FIRDA or TIRDA (frontal or temporal irregular delta activity)] or (iv) the presence of serum autoantibodies, high Tau-protein or dynamic neurofilament light chains (Nfl) abnormalities related to an acute phase of psychiatric symptoms. A definitive autoimmune origin of psychiatric symptoms exists if patients with a subacute or subchronic probable autoimmune-based psychiatric syndrome present and their CSF reveals IgG class autoantibodies. Immunotherapy is an emerging and important topic in the management of autoantibody-associated syndromes. The administration of immunotherapy is advisable for probable and definitive, but not suspected autoimmune-based psychiatric syndromes, as stated recently in published criteria ( 3 ). For this narrative review article on this topic we screened PubMed for the search terms “ antibody immunotherapy psychiatry,” “ autoantibody immunotherapy psychiatry,” “ autoimmune dementia immunotherapy,” “ autoimmune encephalitis immunotherapy,” “ autoimmune psychosis immunotherapy” or “ autoantibody psychosis immunotherapy.” We have included articles in this narrative review that describe case series, observational studies, and randomized placebo-controlled trials between 2010 and 2020 discussing immunotherapy in patients with autoantibodies and psychiatric syndromes in order to attain a reasonably moderate to high evidence level. We therefore decided against focusing on individual case reports published on applying immunotherapy for autoantibody-associated psychiatric syndromes, autoimmune psychosis, and autoimmune dementia. However, for escalating therapy we did look into single case reports and case series, as no other study types have been reported describing such immunotherapies for our patient groups.

Lessons From Immunotherapy in Autoimmune Encephalitis

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 7 ). Second-line immunotherapy consists of rituximab or cyclophosphamide ( 2 , 5 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 ). Alternative therapies are suggested for patients not responding to the aforementioned second-line therapies such as tocilizumab, bortezomib or low-dose interleukin 2 ( 5 7 ). For other drugs that depict a novel escalation treatment strategy such as daratumumab, anti-CD38 antibody-depleting plasma cells seem to alleviate clinical symptoms, but more investigations are required for safety reasons ( 8 ). Results from a large multicenter observational study in 577 patients with N-methyl-D-aspartate-receptor (NMDAR)-encephalitis recommend an early induction of immunotherapy as it could be highly effective and improve the course of the disease ( 9 ). In the study by Titulaer ( 9 ), first-line therapy led to clinical improvement in 251/472 (53%) patients and second-line therapy in 125/221 (56%) patients. Randomized placebo-controlled trial in LGI1 (leucine-rich glioma-inactivated 1) – positive encephalitis patients reported a major benefit regarding cognition and seizures after taking IVIGs compared to placebo treatment in 6/8 (75%) patients ( 4 ). Another large observational study of 103 patients addressed immunotherapy utilizing corticosteroids alone or in combination with either IVIGs or PLEX, and demonstrated a beneficial effect of early immunotherapy concerning seizure frequency and preventing cognitive impairment ( 10 ). In short, the spectrum of therapeutic tools for autoimmune encephalitis is broad and already considered by current national treatment guidelines ( 11 ). Here, a step wise escalation of therapy is preferable, but more clinical placebo-controlled randomized trials in autoimmune encephalitis are needed to compare and validate the efficacy and safety of standard first- and second-line therapies. Several immunological agents are now being carefully investigated, such as the proteasome inhibitor bortezomib in a randomized, multicentric, double blind phase II study in patients with severe autoimmune encephalitis ( 12 ) as the escalation therapy agent. Additional studies also in patients with antibody-associated psychiatric syndromes must be conducted to investigate the efficacy and safety of such immunotherapeutic approaches.

Lessons From Autoimmune Psychosis and Immunotherapy

The first trial was conducted in the United Kingdom (UK) and called SINAPP1 (study of immunotherapy in antibody-positive psychosis: feasibility and acceptability (SINAPPS1)] ( 13 ) at two sites and in 10 patients. IVIGs were administered in 6/10 patients, whereas 4/10 patients underwent PLEX. Immunotherapy resulted in a marked alleviation of psychotic symptoms assessed by PANSS (Positive and Negative Syndrome Scale) indicating that immunotherapy can be administered rapidly and relatively safely in psychiatric clinics ( 13 ). Specific subgroups of patients such as those presenting NMDAR antibodies revealed greater improvement than those with other antibodies such as VGKC complex and GABAAR ( 13 ). Following their encouraging results, they have been conducting a randomized, double-blinded, multicentric, placebo-controlled trial (SINAPPS2) since 2017 (to run until 2021) in the UK. One group undergoes immunotherapy consisting of IVIG and rituximab with additional antipsychotic treatment, and the other gets placebo therapy ( 14 ). Their primary end point is symptomatic remission for 6 months on PANSS observed for a 12-month period ( 14 ). Recent observational studies have indicated that the response to immunotherapy ranges from 67–80% in patients with psychosis ( 15 , 16 ). The response to immunotherapy has been more successful when the disease duration was short and not previously treatment-refractory ( 15 ). Thus, immunotherapy in autoimmune psychosis has been integrated as a therapy recommendation in consensus guidelines according to Pollak et al. ( 17 ).

Lessons From Autoimmune Dementia and Immunotherapy

A large observational study of immunotherapy in 72 patients with presumed autoimmune dementia with progressive and fluctuating cognitive dysfunction based on autoimmunity as revealed by CSF findings and autoantibody detection ( 18 ) showed a strong clinical response to immunotherapy including i. v. methylprednisolone, oral prednisolone, i. v. dexamethasone and IVIGs, as well as PLEX in 46 (64%) of all patients ( 18 ). In addition, the immunotherapeutic success was dependent on an early treatment onset, but also on the type of antibodies and severity of CNS inflammation. Furthermore, there is evidence that continued immunotherapy is highly relevant, as 77% of patients relapsed after it was terminated ( 18 ).

Autoantibody-Associated Psychiatric Syndromes and Immunotherapy

No placebo-controlled randomized studies exist on the efficacy of immunotherapy in autoantibody-associated psychiatric syndromes in adults. We identified two large cohort observational retrospective case series studies describing immunotherapy in autoantibody-associated psychiatric syndromes, although their autoimmune basis is less certain, and the criteria we recently established for autoimmune-based psychiatric disease were not applied. The rationale for applying immunotherapy in such patients with autoantibody-associated psychiatric syndromes is therefore less clear simply because their psychiatric syndromes have not yet be classified relying on their probable autoimmune origin in light of novel criteria ( 3 ). Nevertheless, these two large-scale studies enable an overview of how beneficial immunotherapy is for autoantibody-associated psychiatric syndromes. One such large-scale study by Endres et al. describes immunotherapy in 145 cases of autoantibody-associated psychiatric syndromes ( 19 ), showing that immunotherapy was successful in 94% of 126 patients presenting an autoantibody-associated psychiatric syndrome; steroids proved useful in 106 of 119 (89%) of patients, and 55/126 patients (44%) underwent more than one immunomodulatory treatment, yielding an 89% improvement rate. IVIGs were applied in 55 of 126 (43%) of patients, whereas 42 of 126 (33%) received plasma exchange therapy ( 19 ). Immunotherapy was more beneficial in those patients with autoantibody-associated psychiatric syndromes who presented with autoantibodies against membrane-surface antigens [77 of 80 patients (88%)] compared to those with autoantibodies against intracellular antigens [6/15 patients (40%)] ( 19 ) resembling the findings on patients with autoimmune encephalitis ( 20 22 ). Another large cohort study from the same working group ( 23 ) investigated the occurrence of autoantibody-associated psychiatric disease in patients with schizophrenic and affective psychosis. Thirteen of 24 antibody-positive patients in this large cohort received immunotherapy, and 87% exhibited a good response to immunotherapy which had azathioprine, methotrexate, mycofenolat mofetil, and rituximab. Taken together, these large observational studies ( 19 , 23 ) deliver a low, but consistent evidence level that in those patients with psychiatric syndromes and proven autoantibodies, immunotherapy succeeded in 87–94% of patients ( n = 139). The evidence from these large retrospective case studies supports the usefulness of immunotherapy ( Table 1 ). A recent study of McGinty ( 31 ) seems to be of major interest regarding the application of immunotherapy, as his study revealed a good outcome in autoimmune-epilepsy patients presenting autoantibodies, but no other indices of an autoimmune encephalitis. However, although his work did not address autoantibody-associated psychiatric syndromes, it does question the requirement of an immunotherapy for clinical syndromes associated with autoantibodies in patients not presenting any proof of an underlying encephalitis. Thus, more investigations are necessary comparing the outcomes of patients with autoantibody-associated psychiatric syndromes but no proven encephalitis, with and without immunotherapy.

TABLE 1 Immunotherapy in Autoantibody-Associated Psychiatric Syndromes in Adults Picture 1

Immunotherapy in autoimmune encephalitis and autoimmune-based psychiatric syndromes.

First-Line Immunotherapy in Autoimmune-Based Psychiatric Syndromes

In line with the aforementioned studies ( 19 , 23 ), we recommend immunotherapy ( Figure 1 and Table 1 ) for patients presenting probable or definitive autoimmune-based psychiatric syndromes according to this therapeutic pathway ( Figure 1 and Table 1 ): first-line immunotherapy should include steroids (i. v. or oral), IVIGs, immunoadsorption and/or PLEX. The evidence level for IVIGs in autoimmune encephalitis relies on one randomized trial ( 4 ), but the other therapeutic options rely on an evidence level originating from case series and large observational studies ( 9 , 10 ). We recommend immunotherapy following the careful assessment of specific comorbidities, potential side effects, and patients’ contraindications. Corticosteroids are often the first choice, whereas IVIGs and PLEX are the second option, especially if steroids have been ruled out due to their side effects. Steroids exert multiple effects on the immune system and might thus act on many sites concurrently, such as cytokine modulation ( 32 , 33 ), depleting immune cells such as CD4+ T-cells ( 34 ), and inhibiting immune-cell activity such as macrophagic function ( 35 ). For the above-mentioned immunologic agents’ potential disease mechanisms, see Table 1 . Considering corticosteroids’ mild-to-moderate effects on autoantibody-producing B-cells and blood autoantibodies, combining them with other agents depleting those cells and blood autoantibodies such as PLEX seems advantageous for patients with severe symptoms, but it demonstrates no response to steroids or antibodies against membrane antigens. Another issue to consider when applying steroids: certain populations of psychiatric patients may be more sensitive to additional aggravated or induced depressive, manic, sleep dysfunction, or psychotic symptoms. Therefore, careful monitoring is mandatory when psychiatric patients are undergoing immunotherapy. In addition to steroids, IVIGs are a first-line option to choose for patients presenting the aforementioned side effects from steroids or their contraindications ( Figure 1 and Table 1 ). IVIGs are plasma collected from diverse patients, containing various antibodies suitable for hindering pathogenic T-cells (while they travel through the central nervous system) ( 36 ), and for producing anti-inflammatory effects ( 37 ). To prevent any anaphylactic reaction, only immunoglobulin A (IgA)-deficient patients should not be given IVIGs ( Figure 1 and Table 1 ). PLEX is invasive, and thus the potentially last therapeutic option for first-line immunotherapy. It works by removing blood autoantibodies. First-line immunotherapy with IVIGs and or methlyprednisolone should have failed before applying PLEX. Immunoadsorption is equivalent to PLEX, and seems to have reduced additional CSF antibodies in single case series in patients with autoimmune encephalitis ( 24 ).

FIGURE 1 Immunotherapy in Autoantibody-Associated Psychiatric Syndromes in Adults Picture 2

Clinical pathway for selecting immunotherapy for autoimmune-based psychiatric syndromes. IVIGS/s, intravenous immunoglobulins; IgA, immunoglobulin A; IgG4 subclass, immunoglobulin G4 subclass.

Second-Line Immunotherapy in Autoimmune-Based Psychiatric Syndromes

Second-line therapy should encompass rituximab or cyclophosphamide and is required if first-line therapy fails to show a response within 1 month in autoimmune-based psychiatric syndromes ( Figure 1 and Table 1 ). The evidence level for autoimmune-based psychiatric syndromes is much lower when relying on single cases, that is, those in the retrospective cohort studies of Endres et al. ( 19 , 23 ). The evidence for immunotherapy for patients with autoimmune encephalitis also relies on observational studies and case series. Rituximab is especially beneficial for autoimmune encephalitis patients, as shown in a study by Thompson et al. ( 10 ). As second-line immunotherapy, rituximab should be chosen if autoantibodies are playing a probable immunopathological role (as suspected in NMDAR-positive psychiatric symptoms), as rituximab mainly depletes B-cells via possible mechanisms like (1) cellular toxicity, (2) humoral response activation such as the complement cascade, and/or (3) apoptosis ( 38 40 ). It thus makes sense to apply rituximab in those patients with autoantibody-based psychiatric syndromes and proven membrane-surface autoantibodies such as the NMDAR autoantibody. Rituximab is further recommended if the main immunoglobulin (IgG) subclass detected consists of IgG4 (as proven, for example, in CASPR2-positive or IgLON5-positive encephalitis ( 41 , 42 ). Cyclophosphamide should be the second option after rituximab due to its serious side effects, that is, hemorrhagic cystitis or myelosuppression. However, as it specifically suppresses lymphocyte proliferation, it is also suitable for use in probably T-cell-mediated diseases, eg, autoimmune-based psychiatric symptoms associated with antibodies against intracellular antigens.

Maintenance Immunotherapy in Autoantibody-Based Psychiatric Syndromes

In individual cases of autoantibody-associated psychiatric syndromes, mycophenolate mofetil and azathioprine proved to improve outcome ( 19 ). These agents are suggested for maintenance therapy in steroid-responsive patients. We also recommend mycophenolate mofetil or azathioprine to reserve steroid application for long-term treatment ( Figure 1 and Table 1 ).

Escalation Immunotherapy in Autoantibody-Based Psychiatric Syndromes

Alternative or escalation therapy could entail poorly-investigated substances that have proven beneficial in individual case series or observational studies with specific antibodies such as bortezomib in NMDAR-positive encephalitis ( 28 ), tocilizumab as an interleukin-6 antibody in patients with NMDAR, LGI1 (leucine-rich glioma-inactivated 1) and amphiphysin antibodies ( 26 ) and low-dose interleukin 2 ( 27 ). Note, however, that the evidence level for this kind of immunotherapy is low; furthermore, there is currently no evidence for its administration for autoantibody-associated psychiatric syndromes. Basiliximab is a potentially beneficial interleukin 2 receptor antibody in GAD65-associated encephalitis, as a reduction in cytotoxic CD8+ T-cells in the CSF has been demonstrated ( 43 ). Thus, its application makes sense as experimental therapy for autoimmune-based psychiatric syndroms associated with GAD65 or other antibodies against intracellular antigens. Some agents deserve mention in detail as alternative therapies, although the clinical evidence of benefit is low due to only small case series in autoimmune-encephalitis patients. Tocilizumab is one of these promising candidates, as it impairs interleukin 6-dependent inflammation and inhibits the development of regulatory T cells that play a major role in autoimmune-based neuronal damage ( 44 46 ). It thust seems particularly important to test this substance, especially in those patients with autoimmune-based psychiatric syndromes and proven autoantibodies directed against intracellular antigens. Low dose interleukin 2 is another intriguing candidate, as interleukin 2 regulates the activity of T-cells and provides tolerance over autoimmunity ( 47 ) in autoimmune encephalitis. The proteasome inhibitor bortezomib is another agent to administer in patients presenting severe NMDAR-associated psychiatric symptoms due to autoimmune encephalitis, as several studies have demonstrated ( 28 30 ). We suspect that bortezomib might prove beneficial in autoimmune-based psychiatric syndromes with autoantibodies against membrane-surface antigens. Another intriguing candidate is the humanized anti-CD19 antibody currently being investigated in the NCT04372615 trial in NMDAR encephalitis patients (phase II) as a potential escalating therapy for autoimmune encephalitis in conjunction with suspected B-cell-mediated disease. A recent study showed that an antibody-negative limbic encephalitis patient often revealed a strong CD19+ B-cell response in serum and CSF through fluorescence cell-sorting analysis ( 25 ). In conclusion, as there is currently no evidence for applying these types of experimental escalation therapy for autoimmune-based psychiatric syndromes, more investigations must be carried out to verify their safety, tolerability, and efficacy in our targeted patient collective.


The present review’s main limitation is that the sources of evidence on the administration of immunotherapy for autoantibody-associated psychiatric syndromes is low, and relies on a handful of observatory studies ( 15 , 16 , 19 , 23 ) and guidelines ( 17 ). The experimental therapies suggested for escalation therapy are derived only from single case reports or case series ( 26 28 , 30 , 43 , 48 ) for patients with autoimmune encephalitis. We wish to highlight the low-to-moderate evidence levels, as randomized, placebo-controlled trials are still lacking, as are meta-analyses of patients with autoantibody-associated psychiatric syndromes in general, and those with specifically autoimmune-based psychiatric syndromes.

Ethical Aspects

Immunotherapy in patients with autoimmune-based psychiatric syndromes is an optional and experimental therapy relying on an evidence level IV following case control and cohort studies. Thus, the patient should be well-informed, provide written consent and agree to the treatment on an individual therapeutic trial basis.


Taken together, autoimmune-based psychiatric syndromes have emerged as a novel category of disorders. Immunotherapy is a therapeutic option in autoimmune encephalitis, autoimmune psychosis and autoimmune dementia that should be initiated also in autoimmune-based psychiatric syndromes in analogy to autoimmune encephalitis and autoantibody-associated psychiatric syndromes early to improve the clinical outcome. The early onset of immunotherapy is likely to be relevant to prevent permanently cognitive and behavioral dysfunctions. Lessons from autoimmune encephalitis and psychosis have revealed specific immunotherapeutic agents termed first- and second-line immunotherapies also applied in patients presenting autoantibody-associated psychiatric syndromes. Furthermore, to stabilize and support these patients over the long term, other immunotherapies referred to maintenance or alternative therapy might be administered to severely-affected or drug-refractory patients. Further randomized, placebo-controlled trials are needed to evaluate immunotherapies in patients with autoimmune-based psychiatric syndromes and to prove their efficacy, inferiority or superiority over other immunotherapies. To accelerate and improve the diagnosis-based treatment of autoantibody-associated psychiatric syndromes, an individual, fundamental diagnostic approach must be taken involving CSF, EEG and MRI investigations at psychiatric in- and outpatient institutions and hospitals.

Author Contributions

NH conceived the review and wrote the review draft. CT critically revised the manuscript for important intellectual content. All authors have read and agreed to the published version of the manuscript.


Funding support was received by the Open Access Publication Funds of the Göttingen University.

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


1. Graus F, Titulaer MJ, Balu R, Benseler S, Bien CG, Cellucci T, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol.(2016) 15: 391–404. doi: 10. 1016/S1474-4422(15)00401-9

2. Rössling R, Prüss H. SOP: antibody-associated autoimmune encephalitis. Neurol Res Pract.(2020) 2: 1. doi: 10. 1186/s42466-019-0048-7

3. Hansen N, Lipp M, Vogelgsang J, Vukovich R, Zindler T, Lüdecke D, et al. Autoantibody-associated psychiatric symptoms and syndromes in adults: a narrative review and proposed approach. Brain Behav Immun Health.(2020). 9: 100154. doi: 10. 1016/j. bbih. 2020. 100154

4. Dubey D, Britton J, McKeon A, Gadoth A, Zekeridou A, Lopez Chiriboga SA, et al. Randomized placebo-controlled trial of intravenous immunoglobulin in autoimmune LGI1/CASPR2 epilepsy. Ann Neurol.(2020) 87: 313–23. doi: 10. 1002/ana. 25655

5. Hermetter C, Fazekas F, Hochmeister S. Systematic review: syndromes, early diagnosis, and treatment in autoimmune encephalitis. Front Neurol.(2018) 9: 706. doi: 10. 3389/fneur. 2018. 00706

6. Shin YW, Lee ST, Park KI, Jung KH, Jung KY, Lee SK, et al. Treatment strategies for autoimmune encephalitis. Ther Adv Neurol Disord.(2017) 11: 1756285617722347. doi: 10. 1177/1756285617722347

7. Sell J, Haselmann H, Hallermann S, Hust M, Geis C. Autoimmune encephalitis: novel therapeutic targets at the preclinical level. Expert Opin Ther Targets.(2020). doi: 10. 1080/14728222. 2021. 1856370. [Epub ahead of print].

8. Scheibe F, Ostendorf L, Reincke SM, Prüss H, Brünneck v AC, Köhnlein M, et al. Daratumumab treatment for therapy-refractory anti-CASPR2 encephalitis. J Neurol.(2020) 267: 317–23. doi: 10. 1007/s00415-019-09585-6

9. Titulaer MJ, McCracken L, Gabilondo I, Armangué T, Glaser C, Iizuka T, et al. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol.(2013) 12: 157–65. doi: 10. 1016/S1474-4422(12)70310-1

10. Thompson J, Bi M, Murchison AG, Makuch M, Bien CG, Chu K, et al. Faciobrachial dystonic seizures study group. The importance of early immunotherapy in patients with faciobrachial dystonic seizures. Brain.(2018) 141: 348–56. doi: 10. 1093/brain/awx323

11. Bien C, Ruegg S, Schmutzhard E, Sturzenegger M. Leitlinien für Diagnostik und Therapie in der Neurologie. Immunvermittelte Erkrankungen der grauen Substanz sowie Neurosarkoidose. In: Diener HC, Weimar C, editors. Leitlinien für Diagnostik und Therapie in der Neurologie . Stuttgart: Thieme. (2012).

12. Wickel J, Chung H-Y, Platzer S, Lehmann T, Prüss H, Leypoldt, et al. Generate-boost: study protocol for a prospective, multicenter, randomized controlled, double-blinded phase II trial to evaluate efficacy and safety of bortezomib in patients with severe autoimmune encephalitis. Trials.(2020) 21: 625. doi: 10. 1186/s13063-020-04516-7

13. Lennox BR, Tomei G, Vincent SA, Yeeles K, Pollard R, Palmer-Cooper E, et al. Study of immunotherapy in antibody positive psychosis: feasibility and acceptability (SINAPPS1). J Neurol Neurosurg Psychiatry . (2019) 90: 365–7. doi: 10. 1136/jnnp-2018-318124

14. Lennox B, Yeeles K, Jones PB, Zandi M, Joyce E, Yu LM, Tomei G, et al. Intravenous immunoglobulin and rituximab vs. placebo treatment of antibody-associated psychosis: study protocol of a randomised phase IIa double-blinded placebo-controlled trial (SINAPPS2). Trials.(2019) 20: 331. doi: 10. 1186/s13063-019-3336-1

15. Zandi MS, Deakin JB, Morris K, Buckley C, Jacobson L, Scoriels L, et al. Immunotherapy for patients with acute psychosis and serum N-Methyl D-Aspartate receptor (NMDAR) antibodies: a description of a treated case series. Schizophr Res.(2014) 160: 193–5. doi: 10. 1016/j. schres. 2014. 11. 001

16. Scott JG, Gillis D, Swayne A, Blum S. Testing for antibodies to N-methyl-d-aspartate receptor and other neuronal cell surface antigens in patients with early psychosis. Aust N Z J Psychiatry.(2018) 52: 727–9. doi: 10. 1177/0004867418782421

17. Pollak TA, Lennox BR, Müller S, Benros ME, Prüss H, Tebartz van Elst L, et al. Autoimmune psychosis: an international consensus on an approach to the diagnosis and management of psychosis of suspected autoimmune origin. Lancet Psychiatry.(2020) 7: 93–108. doi: 10. 1016/S2215-0366(19)30290-1

18. Flanagan EP, McKeon A, Lennon VA, Boeve BF, Trenerry MR, Tan KM, et al. Autoimmune dementia: clinical course and predictors of immunotherapy response. Mayo Clin Proc . (2010) 85: 881–97. doi: 10. 4065/mcp. 2010. 0326

19. Endres D, Maier V, Leypoldt F, Wandinger KP, Lennox B, Pollak TA, et al. Autoantibody-associated psychiatric syndromes: a systematic literature review resulting in 145 cases. Psychol Med . (2020) 7: 1–12. doi: 10. 1017/S0033291720002895

20. Frisch C, Malter MP, Elger CE, Helmstaedter C. Neuropsychological course of voltage-gated potassium channel and glutamic acid decarboxylase antibody related limbic encephalitis. Eur J Neurol.(2013) 20: 1297–304. doi: 10. 1111/ene. 12186

21. Hansen N, Widman G, Witt JA, Wagner J, Becker AJ, Elger CE, et al. Seizure control and cognitive improvement via immunotherapy in late onset epilepsy patients with paraneoplastic vs. GAD65 autoantibody-associated limbic encephalits. Epilepsy and Behavior.(2016) 65: 18–24. doi: 10. 1016/j. yebeh. 2016. 10. 016

22. Hansen N, Ernst L, Rüber T, Widman G, Becker AJ, Elger CE, Helmstaedter C. Pre-and long-term postoperative courses of hippocampus-associated memory impairment in epilepsy patients with antibody- associated limbic encephalitis and selective amygdalahippocampectomy. Epilepsy Behav.(2018) 79: 93–9. doi: 10. 1016/j. yebeh. 2017. 10. 033

23. Endres D, Meixensberger S, Dersch R, Feige B, Stich O, Venhoff N, et al. Cerebrospinal fluid, antineuronal autoantibody, EEG, and MRI findings from 992 patients with schizophreniform and affective psychosis. Transl Psychiatry . (2020) 10: 279. doi: 10. 1038/s41398-020-00967-3

24. Dogan Onugoren M, Golombeck KS, Bien C, Abu-Tair M, Brand M, Bulla-Hellwig M, et al. Immunoadsorption therapy in autoimmune encephalitides. Neurol Neuroimmunol Neuroinflamm.(2016) 3: e207. doi: 10. 1212/NXI. 0000000000000207

25. Hansen N, Önder D, Schwing K, Widman G, Leelaarporn P, Prusseit I, et al. CD19+ B-cells in autoantibody-negative limbic encephalitis. Epilepsy Behav.(2020) 106: 107016. doi: 10. 1016/j. yebeh. 2020. 107016

26. Lee WJ, Lee ST, Moon J, Sunwoo JS, Byun JI, Lim JA, et al. Tocilizumab in autoimmune encephalitis refractory to rituximab: an institutional cohort study. Neurotherapeutics.(2016) 13: 824–32. doi: 10. 1007/s13311-016-0442-6

27. Lim JA, Lee ST, Moon J, Jun JS, Park BS, Byun JI, et al. New feasible treatment for refractory autoimmune encephalitis: low-dose interleukin-2. J Neuroimmunol . (2016) 299: 107–11. doi: 10. 1016/j. jneuroim. 2016. 09. 001

28. Scheibe F, Prüss H, Mengel AM, Kohler S, Nümann A, Köhnlein M, et al. Bortezomib for treatment of therapy-refractory anti-NMDA receptor encephalitis. Neurology . (2017) 88: 366–70. doi: 10. 1212/WNL. 0000000000003536

29. Sveinsson O, Granqvist M, Forslin Y, Blennow K, Zetterberg H, Piehl F. Successful combined targeting of B- and plasma cells in treatment refractory anti-NMDAR encephalitis. J Neuroimmunol . (2017) 312: 15–8. doi: 10. 1016/j. jneuroim. 2017. 08. 011

30. Keddie S, Crisp SJ, Blackaby J, Cox A, Coles A, Hart M, et al. Plasma cell depletion with bortezomib in the treatment of refractory N-methyl-d-aspartate (NMDA) receptor antibody encephalitis. Rational developments in neuroimmunological treatment. Eur J Neurol . (2018) 25: 1384–8. doi: 10. 1111/ene. 13759

31. McGinty RN, Handel A, Moloney T, Ramesh A, Fower A, Torzillo E, et al. Clinical features which predict neuronal surface autoantibodies in new-onset focal epilepsy: implications for immunotherapies. J Neurol Neurosurg Psychiatry.(2020). doi: 10. 1136/jnnp-2020-325011. [Epub ahead of print].

32. Danielson M, Reinsfelt B, Westerlind A, Zetterberg H, Blennow K, Ricksten SE. Effects of methylprednisolone on blood-brain barrier and cerebral inflammation in cardiac surgery-a randomized trial. J Neuroinflammation . (2018) 15: 283. doi: 10. 1186/s12974-018-1318-y

33. Miljković Z, Momcilović M, Miljković D, Mostarica-Stojković M. Methylprednisolone inhibits IFN-gamma and IL-17 expression and production by cells infiltrating central nervous system in experimental autoimmune encephalomyelitis. J Neuroinflammation . (2009) 6: 37. doi: 10. 1186/1742-2094-6-37

34. Zuśka-Prot M, Maślanka T. Effect of inhaled and systemic glucocorticoid treatment on CD4 + regulatory and effector T cells in a mouse model of allergic asthma. Int Immunopharmacol . (2017) 45: 98–109. doi: 10. 1016/j. intimp. 2017. 02. 005

35. Xie Y, Tolmeijer S, Oskam JM, Tonkens T, Meijer AH, Schaaf MJM. Glucocorticoids inhibit macrophage differentiation towards a pro-inflammatory phenotype upon wounding without affecting their migration. Dis Model Mech.(2019) 12: dmm037887. doi: 10. 1242/dmm. 037887

36. Othy S, Hegde P, Topçu S, Sharma M, Maddur MS, Lacroix-Desmazes S, et al. Intravenous gammaglobulin inhibits encephalitogenic potential of pathogenic T cells and interferes with their trafficking to the central nervous system, implicating sphingosine-1 phosphate receptor 1-mammalian target of rapamycin axis. J Immunol . (2013) 190: 4535–41. doi: 10. 4049/jimmunol. 1201965

37. Jorgensen SH, Jensen PE, Laursen H, Sorensen PS. Intravenous immunoglobulin ameliorates experimental autoimmune encephalomyelitis and reduces neuropathological abnormalities when administered prophylactically. Neurol Res . (2005) 27: 591–7. doi: 10. 1179/016164105X48798

38. Memon AB, Javed A, Caon C, Srivastawa S, Bao F, Bernitsas E, et al. Long-term safety of rituximab induced peripheral B-cell depletion in autoimmune neurological diseases. PLoS ONE . (2018) 13: e0190425. doi: 10. 1371/journal. pone. 0190425

39. Kosmidis ML, Dalakas MC. Practical considerations on the use of rituximab in autoimmune neurological disorders. Ther Adv Neurol Disord . (2010) 3: 93–105. doi: 10. 1177/1756285609356135

40. Dalakas MC. B-cells as therapeutic targets in autoimmune neurological disorders. Nat Clin Pract Neurol . (2008) 4: 557–67. doi: 10. 1038/ncpneuro0901

41. Irani SR, Pettingill P, Kleopa KA, Schiza N, Waters P, Mazia C, et al. Morvan syndrome: clinical and serological observations in 29 cases. Ann Neurol . (2012) 72: 241–55. doi: 10. 1002/ana. 23577

42. Sabater L, Gaig C, Gelpi E, Bataller L, Lewerenz J, Torres-Vega E, et al. A novel non-rapid-eye movement and rapid-eye-movement parasomnia with sleep breathing disorder associated with antibodies to IgLON5: a case series, characterisation of the antigen, and post-mortem study. Lancet Neurol.(2014) 13: 575–86. doi: 10. 1016/S1474-4422(14)70051-1

43. Widman G, Golombeck K, Hautzel H, Gross CC, Quesada CM, Witt JA, et al. Treating a GAD65 antibody-associated limbic encephalitis with basiliximab: a case study. Front Neurol . (2015) 6: 167. doi: 10. 3389/fneur. 2015. 00167

44. Kang S, Tanaka T, Kishimoto T. Therapeutic uses of anti-interleukin-6 receptor antibody. Int Immunol . (2015) 27: 21–9. doi: 10. 1093/intimm/dxu081

45. Petković F, Lazzarino GP, Engblom D, Blomqvist, A. IL-6R expressed on CNS vascular endothelial cells contributes to the development of experimental autoimmune encephalomyelitis in mice. J Neuroimmunol . (2020) 342: 577211. doi: 10. 1016/j. jneuroim. 2020. 577211

46. Sanchis P, Fernández-Gayol O, Comes G, Escrig A, Giralt M, Palmiter RD, et al. Interleukin-6 derived from the central nervous system may influence the pathogenesis of experimental autoimmune encephalomyelitis in a cell-dependent manner. Cells . (2020) 9: 2. doi: 10. 3390/cells9020330

47. Malek TR, Castro I. Interleukin-2 receptor signaling: at the interface between tolerance and immunity. Immunity . (2010) 33: 153–65. doi: 10. 1016/j. immuni. 2010. 08. 004

48. Lee WJ, Lee ST, Shin YW, Lee HS, Shin HR, Kim DY, et al. Teratoma removal, steroid, IVIG, rituximab and tocilizumab (T-SIRT) in anti-NMDAR encephalitis. Neurotherapeutics.(2020). doi: 10. 1007/s13311-020-00921-7. [Epub ahead of print].

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