A case series of young people treated for neuroimmune mediated mood or psychotic syndromes

This is a special bonus seminar as part of the Department of Psychiatry’s seminar series, with Peter J. Uhlhaas (Charité Universitätsmedizin Berlin) presenting on ‘Gamma-Band Oscillations and Schizophrenia: A Translational and Developmental Perspective’, with Philip McGuire chairing, followed by a presentation from Elizabeth Scott (The University of Sydney), with Naomi Wray chairing.

To join online, please use the Zoom link below: * zoom.us/j/95144715955?pwd=VzNneXVKdms3OEUzQWo2QkE4d1d5Zz09 * Meeting ID: 951 4471 5955 * Passcode: 462130

Our clinical research group has focused on the assessment and active immune treatment of major mood and atypical psychotic syndromes diagnosed as possible ‘autoimmune encephalitis’ (AIE) (indicating acute or subacute onset, marked psychiatric and neurological features, clear evidence on brain imaging, EEG or CSF studies of CNS involvement, and variously associated with brain-specific or other autoantibodies). A case series of 45 young people (mean age 18 years, range 12-28; 41/45 (91%) female) has been assessed, with 43 proceeding to personalized immunotherapy (ie, pulsed high-dose corticosteroids, oral corticosteroids plasma exchange, IVIG, mycophenolate, sirolimus, rituximab). While acute and sub-acute onset was common (over 60%), and major features such as delirium, seizures and other neurological signs were often present, most came to attention as a consequence of non-response to conventional therapies (over 80%), major adverse events from usual treatments or deteriorating course. The majority 32/45 (71%) met international consensus criteria for possible autoimmune encephalitis. EEG (62%), CSF (66%) or brain imaging (77%, including 41% on MRI) abnormalities were frequently detected. Prior to treatment, 78% were not in employment, education, training (NEET). Following therapy, all subjects 38/43 (88%) were rated by the same clinical psychiatrist (ES) as significantly improved (CGI = 1 or 2), the NEET rate fell to 14% and this was associated with an effect size improvement of 2.23 on a standardized assessment of psychosocial function (SOFAs scale). Moderate adverse effects were reported in 8/43 (19%) people and severe adverse effects in 1/43 (2%). While autoantibodies were observed in 31/45 individuals, there were no clear demographic, clinical or response to treatment variables that were associated with the presence or absence of these factors. This case series demonstrates that a subgroup of young people presenting with complex mood and other neuropsychiatric morbidity, marked functional impairment and non-response to conventional treatments (and often without clear evidence of a specific immune mechanism or CNS manifestation of a known systemic syndrome, but with clinical and laboratory factors suggestive of an immune-mediated disorder), respond well to personalized immunotherapy. The need to develop and evaluate enhanced guidelines for clinical assessment and provision of immune therapies is clear.