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Cognitive and Social Functioning Deficits after Anti-N-Methyl-D-Aspartate Receptor Encephalitis: An Exploratory Case Series

Published online by Cambridge University Press:  22 August 2016

Gemma L. McKeon ,
James G. Scott ,
Donna M. Spooner ,
Alexander E. Ryan ,
Stefan Blum ,
David Gillis ,
Daman Langguth  and
Gail A. Robinson
Gemma L. McKeon
Affiliation:
Neuropsychology Research Unit, School of Psychology, The University of Queensland, St Lucia, QLD, Australia The University of Queensland Centre for Clinical Research, Herston, QLD, Australia Child and Youth Mental Health Group, Queensland Centre for Mental Health Research, Wacol, QLD, Australia
James G. Scott
Affiliation:
The University of Queensland Centre for Clinical Research, Herston, QLD, Australia Child and Youth Mental Health Group, Queensland Centre for Mental Health Research, Wacol, QLD, Australia Royal Brisbane and Women’s Hospital, Herston, QLD, Australia
Donna M. Spooner
Affiliation:
Royal Brisbane and Women’s Hospital, Herston, QLD, Australia
Alexander E. Ryan
Affiliation:
The University of Queensland Centre for Clinical Research, Herston, QLD, Australia Child and Youth Mental Health Group, Queensland Centre for Mental Health Research, Wacol, QLD, Australia
Stefan Blum
Affiliation:
The University of Queensland Centre for Clinical Research, Herston, QLD, Australia Princess Alexandra Hospital, Woolloongabba, QLD, Australia
David Gillis
Affiliation:
Royal Brisbane and Women’s Hospital, Herston, QLD, Australia Pathology Queensland, Herston, QLD, Australia
Daman Langguth
Affiliation:
Sullivan Nicolaides Pathology, QLD, Australia
Gail A. Robinson*
Affiliation:
Neuropsychology Research Unit, School of Psychology, The University of Queensland, St Lucia, QLD, Australia The University of Queensland Centre for Clinical Research, Herston, QLD, Australia Royal Brisbane and Women’s Hospital, Herston, QLD, Australia
*
Correspondence and reprint requests to: Gail Robinson, The University of Queensland (UQ), School of Psychology, McElwain Building, UQ, St Lucia, Brisbane, QLD, Australia, 4072. E-mail: g.robinson@psy.uq.edu.au
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Abstract

Background: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a recently described life-threatening autoimmune disorder associated with a characteristic multi-stage neuropsychiatric syndrome. Although it is known that the majority of patients experience neuropsychological disturbance post-treatment, some aspects of the cognitive profile remain unclear. Methods: This study sought to investigate patterns of cognitive functioning in a sample of anti-NMDAR encephalitis patients. Seven (6F:1M; mean age, 26.4 years; range, 16–37 years) treated patients completed a comprehensive set of neurocognitive and social functioning measures. Performance was analyzed using normative data (where available), and comparison with matched controls (10F:4M; mean age, 25.8 years; range, 16–38 years). Results: Individual cognitive profiles ranged from within normal limits to extensive dysfunction. Relative to controls, the patient group’s performance was affected in the domains of verbal/ visual memory, working memory, attention, processing speed, executive functioning, and social cognition. The patient group also reported significantly higher levels of anxiety compared to controls. Conclusions: These results add to the accumulating evidence that neurocognitive deficits, consistent with the distribution and functions of the NMDAR system can persist during recovery from anti-NMDAR encephalitis. This is the first study to provide evidence of performance decrements on measures of social cognition, including some involving theory of mind. (JINS, 2016, 22, 828–838)

Keywords

Anti-N-methyl-D-aspartate receptor encephalitisCognition disordersNeuropsychologySocial behaviorTheory of mindTreatment outcome

Information

Type
Research Articles
Information
Journal of the International Neuropsychological Society , Volume 22 , Issue 8 , September 2016 , pp. 828 - 838
Copyright
Copyright © The International Neuropsychological Society 2016 

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References

Bach, L.J. (2014). Long term rehabilitation management and outcome of anti-NMDA receptor encephalitis: Case reports. NeuroRehabilitation, 35(4), 863–875. doi:10.3233/NRE-141176 Google Scholar
Baird, A., Dewar, B., Critchley, H., Dolan, R., Shallice, T., & Cipolotti, L. (2006). Social and emotional functions in three patients with medial frontal lobe damage including the anterior cingulate cortex. Cognitive Neuropsychiatry, 11(4), 369–388. doi:10.1080/13546800444000245 CrossRefGoogle ScholarPubMed
Baron-Cohen, S., Jolliffe, T., Mortimore, C., & Robertson, M. (1997). Another advanced test of theory of mind: Evidence from very high functioning adults with autism or asperger syndrome. Journal of Child Psychology and Psychiatry, 38(7), 813–822.CrossRefGoogle ScholarPubMed
Baron-Cohen, S., Wheelwright, S., Hill, J., Raste, Y., & Plumb, I. (2001). The ‘Reading the Mind in the Eyes’ Test revised version: A study with normal adults, and adults with asperger syndrome or high-functioning autism. Journal of Child Psychology and Psychiatry, 42(2), 241–251.CrossRefGoogle ScholarPubMed
Blair, R.J.R., & Cipolotti, L. (2000). Impaired social response reversal: A case of ‘acquired sociopathy’. Brain, 123, 1122–1141.Google Scholar
Bliss, T.V.P., & Collingridge, G.L. (1993). A synaptic model of memory: Long-term potentiation in the hippocampus. Nature, 361, 31–39.Google Scholar
Burgess, P., & Shallice, T. (1997). The Hayling and Brixton Tests. Edmonds, UK: Thames Valley Test Company.Google Scholar
Craig, J.S., Hatton, C., Craig, F.B., & Bentall, R.P. (2004). Persecutory beliefs, attributions and theory of mind: Comparison of patients with paranoid delusions, Asperger’s syndrome and healthy controls. Schizophrenia Research, 69, 29–33. doi:10.1016/S0920-9964(03)00154-3 CrossRefGoogle ScholarPubMed
Crawford, J.R., & Garthwaite, P.H. (2002). Investigation of the single case in neuropsychology: Confidence limits on the abnormality of test scores and test score differences. Neuropsychologia, 40, 1196–1208.CrossRefGoogle ScholarPubMed
Crawford, J.R., & Howell, D.C. (1998). Comparing an individual’s test score against norms derived from small samples. The Clinical Neuropsychologist, 12(4), 482–486.CrossRefGoogle Scholar
Creten, C., van der Zwaan, S., Blankespoor, R.J., Maatkamp, A., Nicolai, J., van Os, J., & Schieveld, J.N.M. (2011). Late onset autism and anti-NMDA-receptor encephalitis. Lancet, 378, 98.Google Scholar
Dalmau, J., Gleichman, A.J., Hughes, E.G., Rossi, J.E., Peng, X., Lai, M., & Lynch, D.R. (2008). Anti-NMDA-receptor encephalitis: Case series and analysis of the effects of antibodies. Lancet Neurology, 7, 1091–1098. doi:10.1016/S1474-422(08)70224-2 CrossRefGoogle ScholarPubMed
Dalmau, J., Lancaster, E., Martinez-Hernandez, E., Rosenfeld, M.R., & Balice-Gordon, R. (2011). Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurology, 10, 63–74.CrossRefGoogle ScholarPubMed
Dalmau, J., & Rosenfeld, M.R. (2014). Autoimmune encephalitis update. Neuro-Oncology, 16(6), 771–778. doi:10.1093/neuonc/nou030 Google Scholar
Dalmau, J., Tuzun, E., Wu, H., Masjuan, J., Rossi, J.E., Voloschin, A., & Lynch, D.R. (2007). Paraneoplastic Anti-N-methyl-D-aspartate Receptor encephalitis associated with ovarian teratoma. Annals of Neurology, 61, 25–36. doi:10.1002/ana.21050 Google Scholar
Delis, D.C., Kaplan, E., & Kramer, J.H. (2001). Delis-Kaplan Executive Function System (D-KEFS) Examiner’s Manual. San Antonio, TX: The Psychological Corporation.Google Scholar
Finke, C., Kopp, U.A., Pajkert, A., Behrens, J.R., Leypoldt, F., Wuefel, J.T., & Paul, F. (2015). Structural hippocampal damage following anti-N-methyl-D-aspartate receptor encephalitis. Biological Psychiatry, 79, 727–734. doi:10.1016/j.biopsych.2015.02.024 CrossRefGoogle ScholarPubMed
Finke, C., Kopp, U.A., Pruss, H., Dalmau, J., Wandinger, K., & Ploner, C.J. (2012). Cognitive deficits following anti-NMDA receptor encephalitis. Journal of Neurology, Neurosurgery, and Psychiatry, 83, 195–198. doi:10.1136/jnnp-2011-300411 CrossRefGoogle ScholarPubMed
Finke, C., Kopp, U.A., Scheel, M., Pech, L., Soemmer, C., Schlichting, J., & Paul, F. (2013). Functional and structural brain changes in anti-N-methyl-D-aspartate receptor encephalitis. Annals of Neurology, 74, 284–296.CrossRefGoogle ScholarPubMed
Florance, N.R., Davis, R.L., Lam, C., Szperka, C., Zhou, L., Ahmad, S., & Dalmau, J. (2009). Anti-N-Methyl-D-Aspartate receptor (NMDAR) encephalitis in children and adolescents. Annals of Neurology, 66, 11–18. doi:10.1002/ ana.21756 Google Scholar
Goodglass, H., Kaplan, E., & Barresi, B. (2000). The Boston Diagnostic Aphasia Examination: Third edition. Philadelphia, PA: Lippincott Williams & Wilkins.Google Scholar
Heims, H.C., Critchley, H.D., Dolan, R., Mathias, C.J., & Cipolotti, L. (2004). Social and motivational functioning is not critically dependent on feedback of autonomic responses: Neuropsychological evidence from patients with pure autonomic failure. Neuropsychologia, 42, 1979–1988. doi:10.1016/j.neuropsychologia.2004.06.001 Google Scholar
Howard, D., & Patterson, K. (1992). The pyramids and palm trees test. Edmonds, UK: Thames Valley Test Company.Google Scholar
Hughes, E.G., Peng, X., Gleichman, A.J., Lai, M., Zhou, L., Tsou, R., & Balice-Gordon, R. (2010). Cellular and synaptic mechanisms of anti-NMDA receptor encephalitis. The Journal of Neuroscience, 30(17), 5866–5875. doi:10.1523/JNEUROSCI.0167-10.2010 CrossRefGoogle ScholarPubMed
Hunt, D.L., & Castillo, P.E. (2012). Synaptic plasticity of NMDA receptors: Mechanisms and functional implications. Current Opinion in Neurobiology, 22, 496–508. doi:10.1016/j.conb.2012.01.007 CrossRefGoogle ScholarPubMed
Iizuka, T., Yoshii, S., Kan, S., Hamada, J., Dalmau, J., Sakai, F., & Mochizuki, H. (2010). Reversible brain atrophy in anti-NMDA receptor encephalitis: A long-term observational study. Journal of Neurology, 257, 1686–1691. doi:10.1007/s00415-010-5604-6 Google Scholar
Irani, S.R., Bera, K., Waters, P., Zuliani, L., Maxwell, S., Zandi, M.S., & Vincent, A. (2010). N-methyl-D-aspartate antibody encephalitis: Temporal progression of clinical and paraclinical observations in a predominantly non-paraneoplastic disorder of both sexes. Brain, 133, 1655–1667. doi:10.1093/brain/awq113 Google Scholar
Kettle, J.W.L., O’Brien-Simpson, L., & Allen, N.B. (2008). Impaired theory of mind in first-episode schizophrenia: Comparison with community, university and depressed controls. Schizophrenia Research, 99, 96–102. doi:10.1016/j.schres.2007.11.011 Google Scholar
Lahera, G., Benito, A., Montes, J.M., Fernandez-Liria, A., Olbert, C.M., & Penn, D.L. (2013). Social Cognition and Interaction Training (SCIT) for outpatients with bipolar disorder. Journal of Affective Disorders, 146, 132–136. doi:10.1016/j.jad.2012.06.032 Google Scholar
Matricardi, S., Patrini, M., Freri, E., Ragona, F., Zibordi, F., Andreetta, F., & Granata, T. (2016). Cognitive and neuropsychological evolution in children with anti-NMDAR encephalitis. Journal of Neurology, 263, 765–771. doi:10.1007/s00415-016-8056-9 Google Scholar
Meyers, J.E., & Meyers, K.R. (1996). Rey Complex Figure Test and Recognition Trial. Lutz, FL: Psychological Assessment Resources, Inc.Google Scholar
Moscato, E.H., Jain, A., Peng, X., Hughes, E.G., Dalmau, J., & Balice-Gordon, R. (2010). Mechanisms underlying autoimmune synaptic encephalitis leading to disorders of memory, behavior and cognition: Insights from molecular, cellular and synaptic studies. European Journal of Neuroscience, 32, 298–309. doi:10.1111/j.1460-9568.2010.07349.x Google Scholar
Moscato, E.H., Peng, X., Jain, A., Parsons, T.D., Dalmau, J., & Balice-Gordon, R. (2013). Acute mechanisms underlying antibody effects in anti-N-methyl-D-aspartate receptor encephalitis. Annals of Neurology, 76, 108–119. doi:10.1002/ana.24195 Google Scholar
Murphy, D. (2006). Theory of mind in Asperger’s syndrome, schizophrenia and personality disordered forensic patients. Cognitive Neuropsychiatry, 11(2), 99–111. doi:10.1080/13546800444000182 Google Scholar
Pashler, H. (1994). Dual-task interference in simple tasks: Data and theory. Psychological Bulletin, 116(2), 220–244.Google Scholar
Patel, N., Rao, V.A., Heilman-Espinoza, E.R., Lai, R., Quesada, R.A., & Flint, A.C. (2012). Simple and reliable determination of the Modified Rankin Scale score in neurosurgical and neurological patients. Neurosurgery, 71, 971–975. doi:10.1227/NEU.0b013e31826a8a56 Google Scholar
Penn, D.L., Roberts, D.L., Combs, D., & Sterne, A. (2007). The development of the Social Cognition and Interaction Training Program for schizophrenia spectrum disorders. Psychiatric Services, 58(4), 449–451.Google Scholar
Roberts, D.L., & Penn, D.L. (2009). Social Cognition and Interaction Training (SCIT) for outpatients with schizophrenia: A preliminary study. Psychiatry Research, 166, 141–147. doi:10.1016/j.psychres.2008.02.007 Google Scholar
Robertson, I.H., Manly, T., Andrade, J., Baddeley, B.T., & Yiend, J. (1997). ‘Oops!’: Performance correlates of everyday attentional failures in traumatic brain injured and normal subjects. Neuropsychologia, 35(6), 747–758.Google Scholar
Robinson, G.A., Cipolotti, L., Walker, D.G., Biggs, V., Bozzali, M., & Shallice, T. (2015). Verbal suppression and strategy use: A role for the right lateral prefrontal cortex? Brain, 138, 1084–1096.CrossRefGoogle ScholarPubMed
Snaith, R.P., & Zigmond, A.S. (1994). The Hospital Anxiety and Depression Scale: Manual. London, UK: GL Assessment.Google Scholar
Tham, S., & Kong, K. (2012). A case of anti-NMDAR (N-methyl-D-aspartate receptor) encephalitis: A rehabilitation perspective. NeuroRehabilitation, 30, 109–112. doi:10.3233/NRE-2012-0733 Google Scholar
Titulaer, M.J., McCracken, L., Gabilondo, I., Armangue, T., Glaser, C., Iizuka, T., & Dalmau, J. (2013). Treatment and prognostic factors for long-term outcome in patients with anti-NMDA encephalitis: An observational cohort study. Lancet Neurology, 12, 157–165. doi:10.1016/S1474-4422(12)70310-1 Google Scholar
van Harskamp, N.J., Rudge, P., & Cipolotti, L. (2005). Cognitive and social impairments in patients with superficial siderosis. Brain, 128, 1082–1092. doi:10.1093/brain/awh487 Google Scholar
Warrington, E.K. (1997). The Graded Naming Test: A restandardisation. Neuropsychological Rehabilitation, 7(2), 143–146.Google Scholar
Waxman, E.A., & Lynch, D.R. (2005). N-methyl-D-aspartate receptor subtypes: Multiple roles in excitotoxicity and neurological disease. Neuroscientist, 11(1), 37–49. doi:10.1177/1073858404269012 Google Scholar
Wechsler, D. (2009). Advanced clinical solutions for WAIS-IV and WMS-IV: Administration and scoring manual. New York: Pearson Assessment.Google Scholar
Wechsler, D., Coalson, D.L., & Engi Raiford, S. (2008). Wechsler Adult Intelligence Scale, Fourth Edition (WAIS-IV) Technical and Interpretive Manual. San Antonio, TX: NCS Pearson Inc.Google Scholar
Wechsler, D., Holdnack, J.A., & Whipple Drozdick, L. (2009). Wechsler Memory Scale, Fourth Edition (WMS-IV) Technical and Interpretive Manual. San Antonio, TX: NCS Pearson Inc.Google Scholar
Wechsler, D., & Zhou, X. (2011). Wechsler Abbreviated Scale of Intelligence - Second Edition (WASI-II): Manual. San Antonio, TX: NCS, Person, Inc.Google Scholar
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