Clinical characterisation of patients in the post-acute stage of anti-NMDA receptor encephalitis: a prospective cohort study and comparison with patients with schizophrenia spectrum disorders
Mar Guasp1, Mireia Rosa-Justicia2, Amaia Muñoz-Lopetegi3, Eugenia Martinez-Hernandez4, Thais Armangue5, Gisela Sugranyes2, Heike Stein6, Laia Prades2, Helena Ariño2, Jesús Planagumà2, Elena De La Serna2, Domingo Escudero2, Sara Llufriu7, Raquel Sánchez-Valle7, Joan Santamaria3, Albert Compte2, Josefina Castro-Fornieles7, Josep Dalmau2
1Hospital Clínic Barcelona - IDIBAPS, 2IDIBAPS, 3Hospital Clinic of Barcelona, 4IDIBAPS- Hospital Clinic, 5IDIBAPS-HClinic, 6Laboratoire de Neurosciences Cognitives et Computationnelles, 7Hospital Clínic Barcelona
Objective:
To characterize the clinical features of the post-acute stage of anti-NMDAR encephalitis (NMDARe), the similarities with schizophrenia spectrum disorders (SCZ), and the factors that predict cognitive-psychiatric outcomes.
Background:
NMDARe is associated with protracted symptoms during a post-acute stage that is not well known.
Design/Methods:
In this prospective observational study, patients in the post-acute stage of NMDARe underwent 3 visits (V1, study entry; V2, 6 months; V3, 12 months) including comprehensive neuropsychiatric evaluations at Hospital Clínic, Barcelona. SCZ patients and healthy participants (HC) undertook similar evaluations. Linear mixed-effect models served to assess longitudinal differences in measures.
Results:
28 NMDARe, 27 SCZ, and 27 HC were recruited. Although, by V1 (median 4 months [IQR 3–7] from disease onset), many acute-stage NMDARe symptoms had resolved (acute stage median mRS 5 [IQR 4–5] vs V1 mRS [1–2]; p<0.0001), 89% of patients showed deficits in ≥1 cognitive domain (CD). In NMDARe, 15/22 (68%) CD variables were impaired at V1, whereas only 8/22 (36%) were altered at V3 (p=0.016). In SCZ, 11/22 (50%) variables (all shared with NMDARe) were impaired at V1, without changes at V3. Two acute-stage NMDARe features (decreased consciousness; no improvement within first 4 weeks of treatment) predicted CD outcomes, and a visuospatial task (serial biases) at V1 showed potential in predicting learning and memory outcomes. At V1, all psychiatric symptom clusters were similarly altered in NMDARe and SCZ, but only NMDARe subsequently improved (p=0.031). The greatest NMDARe cognitive-psychiatric improvement occurred between V1-V2. During this interval, 14% NMDARe patients would have met the diagnostic criteria of schizophrenia if CSF antibody findings had not been investigated.
Conclusions:
The cognitive-psychiatric symptoms of post-acute NMDARe resembled those of stabilized schizophrenia, but only NMDARe patients progressively improved, predominantly during V1-V2. These findings are important for clinical trials on NMDARe and suggest that prompt cognitive-psychosocial rehabilitation may be valuable.