Abstract: "Objectives Document phenotypes and treatment outcomes including psychiatric sequelae in NMDAR-Ab encephalitis Background Since the initial description by Dalmau et al in 2005 the phenotype of NMDAR-Ab encephalitis has broadened to include patients with a more limited clinical spectrum. Methods Retrospective chart review of patients with NMDAR-Ab-associated disease managed in a single quaternary referral centre. Results The files of 25 patients with NMDAR-Abs (scores 1-4 by cell-based assay) were reviewed. Median follow-up was 33 months. "Typical" cases (n=16, M:F 7:9, age 13-37, 1 teratoma, 1 thyroid cancer) were all fulminant over months and all except one were treated with immunotherapy within 6 weeks of onset of symptoms. Modified Rankin scale (mRS) scores at maximum were 3-5 (median 5). Sixteen received corticosteroids; 13/16 were also given IVIg/PEx and 2/16 were subsequently given cyclophosphamide or rituximab. Outcome scores were 0-3, median 1. The nine "atypical" patients (M:F 5:4, age 12-77, no tumours detected) had variable presentations that included psychosis or depression, movement disorders or seizures. Seven received steroids and three also IVIg/PEx; two received only symptomatic treatments. Maximum mRS scores were 2-4 median 2 (7 managed as outpatients) and 0-3, median 1 after treatment. Seven patients from the whole cohort have residual psychiatric disturbance with anxiety and depression. Although the maximum mRS scores were higher (p<0.001) in the typical than atypical patients , the routine NMDAR-Ab scores at maximum and follow-up, and the final mRS scores did not differ between the typical and atypical patients. Conclusion: The clinical phenotypes associated with NMDAR-Abs include typical younger patients and atypical older patients, often with unexplained psychiatric features. Immunotherapy remains important in returning patients to high function. Routine antibody screening before treatment does not discriminate between the two groups, and final outcomes are good overall, but persistent obsessive or anxiety spectrum disorders are common."

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Abstract: "Autoimmune encephalitides can present with altered mental states, particularly psychosis and delirium. Psychiatrists need to be particularly vigilant in cases of first-episode psychosis and to look out for other, sometimes subtle, features of encephalitis. Encephalitis related to N-methyl-D-aspartate (NMDA) receptor autoantibodies is the most common autoimmune cause of isolated psychosis, the second being related to voltage-gated potassium channel (VGKC)-complex antibodies. Psychiatrists should note ‘red flag’ signs of seizures, autonomic instability, movement disorders and sensitivity to antipsychotic medication (including neuroleptic malignant syndrome). They should also be aware that, in some cases, encephalitis is a non-metastatic manifestation of malignancy. Treatment primarily involves suppression of immunity and is often successful if delivered early. There is accumulating evidence that isolated psychiatric syndromes can be caused by autoimmunity and this could potentially signal a significant change in the approach to disorders such as schizophrenia. Psychiatrists and neurologists need to work together to diagnose, manage and understand this group of conditions."

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Abstract: "In 2007, serum IgG autoantibodies to the NMDAR (NMDAR-Ab) were identified in subjects with an autoimmune encephalopathy responsive to immunotherapy; two thirds of whom present with psychiatric symptoms (Dalmau et al., 2007; Irani et al., 2010; Titulaer et al., 2013). There is increasing evidence for NMDAR-hypofunction and neuroinflammation in the pathophysiology of first episode schizophrenia (Kahn and Sommer, 2014). Whilst many patients with NMDAR-ab develop a widespread encephalopathy, restricted phenotypes, including isolated psychosis, epilepsy, or movement disorders have also been described (Irani et al., 2010; Zandi et al., 2011; Brenner et al., 2013; Titulaer et al., 2013; Hacohen et al., 2014)."

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Abstract: "Objective There are now a large number of requests for N-methyl-D-aspartate receptor autoantibody (NMDAR-Ab) tests, and it is important to assess the clinical relevance of all results, particularly when they are reported as ‘Low Positive’. Methods The clinical data of 56 patients found Positive or Low Positive by the Oxford live cell-based assay were reviewed. An autoimmune basis for the condition was assigned as ‘Definite’, ‘Possible’ or ‘Unlikely’. The number of core features (encephalopathy, psychiatric, cognitive, epileptic, extrapyramidal and inflammatory cerebrospinal fluid (CSF)) was tabulated. Results Twenty-five (44.6%) patients had a Definite NMDAR-Ab encephalitis (eight ovarian teratomas, one Hodgkin's lymphoma), 18 (32.1%) a Possible NMDAR-Ab encephalitis and 13 (23.2%) an Unlikely autoimmune syndrome. Serum NMDAR-Ab levels were higher in patients with tumours. Positive NMDAR-Abs were found not only in patients with three or more core features and a Definite syndrome, but also in five patients classified as Possible. Conversely, Low Positive NMDAR-Abs were present in 7 Definite cases as well as in 13 Possible cases. Unlikely patients had mainly Low Positive antibodies and fewer core features. CSF NMDAR-Abs, only available in 11 pairs and at varying time points, broadly related to serum levels and were Positive in 3/3 patients with tumours but in only 2/5 Definite patients, and none of the Possible or Unlikely cases. Interpretation Using live cell-based assays, Positive and Low Positive antibodies can be of clinical significance. The number of core clinical features should help to select those patients in whom an immunotherapy intervention might be considered, irrespective of the antibody level."

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Abstract: "In this article we report recent interesting diagnostic and therapeutic advances in a diverse range of movement disorders with associated psychiatric comorbidity. Areas discussed include social cognition in Huntington disease, neuroimaging of functional movement disorders, treatment of psychosis in Parkinson disease, new advances in autoimmune disease, and management of Tourette syndrome."

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Abstract: "In this update, we review recent advances in antibody-associated disorders of the central nervous system, and the immune mechanisms which may contribute to Alzheimer’s disease, traumatic brain injury and schizophrenia. The field of neuroimmunology is rapidly developing and has concerned itself with an expanding portfolio of diseases. The core neuroimmunological diseases remain, multiple sclerosis, neuromyelitis optica, primary inflammatory and antibody-associated disorders of the central and peripheral nervous system (including Myasthenia Gravis and other disorders of neuromuscular junction and muscle, paraneoplastic syndromes, paraproteinaemic neuropathies), and the neurological involvement seen in systemic inflammatory diseases including lupus, sarcoidosis and vasculitis. But it is increasingly realised that immune mechanisms may contribute to the pathogenesis of degenerative diseases including Alzheimer’s disease, traumatic brain disease and psychiatric diseases including schizophrenia and depression. These common and devastating disorders, often without effective disease-modifying therapies, are yet to be seen in a conventional neuroimmunology clinic, but the immune mechanisms identified have encouraged research into novel therapeutic approaches for them."

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Abstract: "Autoimmune encephalitis associated with antibodies to leucine-rich glioma inactivated 1 (LGI1) is recently described and there is a lack of detailed reports on the treatment of relapsing or refractory cases and long-term outcomes. Two case reports are presented. Both cases had faciobrachial dystonic seizures (FBDS) and received rituximab after relapsing or refractory disease. Both cases achieved sustained clinical remission of up to 15 and 56 months respectively. Rituximab use allowed withdrawal of corticosteroids and was well tolerated. Randomized clinical trials are needed in LGI1 encephalitis and other autoimmune encephalitides."

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Abstract: "This review concentrates on the evidence for autoantibodies to cell surface synaptic proteins in psychosis and schizophrenia. We and others have recently found antibodies to the N-methyl-D-aspartate receptor in first-episode psychosis. We describe the evidence for pathogenicity and disease-relevance of these antibodies, which builds on the novel field in neuroimmunology of cell surface antibody–associated central nervous system disorders. Relevant autoantibodies in psychosis and schizophrenia are likely to be those directed to cell surface proteins, in which the likelihood of pathogenicity is greater. We discuss the evidence for this from the field of paraneoplastic neurologic syndromes and the discovery of novel cell surface antigen central nervous system autoimmune syndromes."

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