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      Anti-NMDA-receptor encephalitis presenting with catatonia and neuroleptic malignant syndrome in patients with intellectual disability and autism

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          Abstract

          We report anti- N-methyl- d-aspartate (NMDA) receptor encephalitis in two patients with autism and intellectual disability presenting with neuropsychiatric symptoms of catatonia and neuroleptic malignant syndrome. Case reports such as these help raise awareness of this clinical issue. By paving the way for earlier diagnoses they ultimately maximise the potential for curative treatments and prevention of long-term complications.

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          Evidence for antibody-mediated pathogenesis in anti-NMDAR encephalitis associated with ovarian teratoma.

          Erdem Tuzun, Lei Zhou, Joachim M Baehring … (2009)
          We report the immunopathological analysis of the brain and tumor of two patients who died of anti-NMDAR-associated encephalitis, and of the tumor of nine patients who recovered. Findings included prominent microgliosis and deposits of IgG with rare inflammatory infiltrates in the hippocampus, forebrain, basal ganglia, and spinal cord. Detection of cells expressing markers of cytotoxicity (TIA, granzyme B, perforin and Fas/Fas ligand) was extremely uncommon. All tumors showed NMDAR-expressing neurons and inflammatory infiltrates. All patients’ NMDAR antibodies were IgG1, IgG2, or IgG3. No complement deposits were observed in any of the central nervous system regions examined. Overall, these findings coupled with recently reported in vitro data showing that antibodies downregulate the levels of NMDA receptors suggest that the antibody immune-response is more relevant than cytotoxic T-cell mechanisms in the pathogenesis of anti-NMDAR-associated encephalitis.
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            Cognitive deficits following anti-NMDA receptor encephalitis.

            Carsten Finke, Ute A Kopp, Harald Prüss … (2012)
            Anti-NMDA receptor (NMDAR) encephalitis is a recently characterised autoimmune disorder mainly affecting young women. Although the clinical features of the acute disease are well characterised, cognitive long-term outcome has not been examined in detail. The authors investigated cognitive performance in nine patients with proven anti-NMDAR encephalitis after recovery from the acute disease period (median 43 months after disease onset, range 23 to 69). Patients underwent a comprehensive neuropsychological assessment, including memory tasks that have previously been shown to be sensitive for hippocampal dysfunction. Substantial persistent cognitive impairments were observed in eight out of nine patients that mainly consisted of deficits in executive functions and memory. The severity of these deficits varied inter-individually. Patients with early immunotherapy performed significantly better. The most severe deficits were observed with inefficient or delayed initial treatment. Our results suggest that cognitive deficits constitute a major long-term morbidity of anti-NMDAR encephalitis. These deficits relate to the distribution of NMDARs in the human brain and their functional role in normal cognition. Good cognitive long-term outcome may depend on early and aggressive treatment.
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              Anti-NMDA-receptor encephalitis: a severe, multistage, treatable disorder presenting with psychosis.

              Klaus-Peter Wandinger, Josep Dalmau, Sandra Saschenbrecker … (2011)
              Anti-NMDA-receptor encephalitis is a severe, treatable and potentially reversible disorder presenting with memory deficits, psychiatric symptoms and seizures. Initially described in young patients with ovarian teratoma, the disease is meanwhile increasingly recognized also in women without tumours, in men and in children. The presence of anti-glutamate receptor (type NMDA) autoantibodies in serum or cerebrospinal fluid is specific for this novel and widely underdiagnosed disorder. Early recognition is crucial since prognosis largely depends on adequate immunotherapy and, in paraneoplastic cases, complete tumour removal. Indirect immunofluorescence using NMDA-type glutamate receptors recombinantly expressed in human cells is a highly competent method for diagnosing anti-NMDA-receptor encephalitis. Copyright © 2010 Elsevier B.V. All rights reserved.
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                Author and article information

                Journal
                Journal ID (nlm-ta): BJPsych Bull
                Journal ID (iso-abbrev): BJPsych Bull
                Journal ID (hwp): pbrcpsych
                Title: BJPsych Bulletin
                Publisher: Royal College of Psychiatrists
                ISSN (Print): 2056-4694
                ISSN (Electronic): 2056-4708
                Publication date (Print): February 2015
                Volume: 39
                Issue: 1
                Pages: 32-35
                Affiliations
                [1 ]Adult Learning Disability Service, Leicestershire Partnership NHS Trust
                [2 ]Department of Medical Education, School of Medicine, University of Leicester
                [3 ]Department of Neurology, University Hospitals of Leicester
                [4 ]University of Leicester
                Author notes
                Correspondence to Reza Kiani ( Reza.Kiani@ 123456leicspart.nhs.uk )

                Reza Kiani (MD, Dip, MRCPsych) is a consultant in adult learning disability psychiatry, a core educational tutor for Leicestershire Partnership NHS Trust and a clinical teacher in the Department of Medical Education, School of Medicine, University of Leicester. Mark Lawden (PhD, FRCP), Penelope Eames (MD, MRCP), Peter Critchley (MD, FRCP) are consultant neurologists at the Department of Neurology, University Hospitals of Leicester. Sabyasachi Bhaumik (OBE, FRCPsych) is an honorary professor in psychiatry at the University of Leicester and a consultant psychiatrist for the Leicestershire Partnership NHS Trust. Sunita Odedra (BSc) is a final year medical student at the University of Leicester. Rohit Gumber (MBChB, MRCPsych) is a consultant psychiatrist in the Adult Learning Disability Service, Leicestershire Partnership NHS Trust.

                Article
                DOI: 10.1192/pb.bp.112.041954
                PMC ID: 4495827
                SO-VID: 3c3833f3-d3ee-414c-a78c-cbac0226989f
                Copyright © © 2014 The Royal College of Psychiatrists
                License:

                This is an open-access article published by the Royal College of Psychiatrists and distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 11 November 2012
                Date accepted : 13 December 2012
                Categories
                Subject: Current Practice

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