Younger Age at Onset Is Associated With Worse Long-term Behavioral Outcomes in Anti-NMDA Receptor Encephalitis

Abstract

Background and ObjectivesAnti-NMDA receptor encephalitis (anti-NMDARE) is one of the most common causes of encephalitis. It typically presents in adolescence and young adulthood, but little is known about its potential long-term consequences across the lifespan. Adaptive behavior describes an individual's ability to respond and adapt to environmental demands and unanticipated changes in daily routines. In this study, we evaluate the relationship between features from clinical presentation, including age, and long-term adaptive behavior in participants with anti-NMDARE.MethodsCross-sectional informant-reported data were collected between 2017 and 2019 from 41 individuals/caregivers of individuals with anti-NMDARE treated at 3 major academic hospitals. Neurologic disability was assessed by record review using the modified Rankin Scale (mRS). Functional outcomes were assessed using the validated Adaptive Behavior Assessment System, Third Edition (ABAS-3).ResultsThe mean age at the time of study enrollment was 23.4 years (SD 17.0 years), and the mean time from symptom onset to study enrollment was 4.0 years. Seventeen participants were aged <12 years at symptom onset, 19 participants were aged 12–30 years, and 5 participants were aged >30 years. Mean ABAS-3 scores at study enrollment for all participants were in the average range (mean general adaptive composite standard score 92.5, SD 18.7). Individuals aged <12 years at symptom onset had lower mean ABAS-3 scores and were in the below average range compared with those aged 12–30 years at symptom onset, whose mean scores were in the average range (87 vs 99, p < 0.05). Similar differences were seen in 3 of the individual subscales (functional academics, health and safety, and self-care). There were no significant differences in mRS scores between age groups (p > 0.05).DiscussionAlthough anti-NMDARE is associated with an overall favorable outcome, younger age at onset associates with worse long-term adaptive behavior despite no differences in neurologic disability. These findings suggest that the disease may have distinct consequences on the early developing brain. Future studies should evaluate behavioral recovery and quality of life after anti-NMDARE and identify additional factors associated with differential recovery.

Disease course and psychosocial outcome for children and adolescents with anti-N-methyl-D-aspartate receptor encephalitis

“…In two patients the fatigue is mild, but in one patient it is severe and enables her to pursue her hobbies. Fatigue has been recurrently described as a residual symptom in 27–80% of patients after anti-NMDARE (Blum et al, 2020; de Bruijn et al, 2018; Tomlinson et al, 2020; Yeshokumar et al, 2022) and in one of these studies fatigue was linked to a poorer QoL (de Bruijn et al, 2018). Disease related fatigue is often multifactorial and difficult to manage, but can have an important impact on quality of life and daily functioning (Hersche et al, 2022).…”

Long-term effects of anti-N-methyl-d-aspartate receptor encephalitis on quality of life

“…McKeon’s study first demonstrated deficits in social functioning during the post-acute-phase in patients with NMDARE, evidence of impaired performance on social cognition tasks ( 31 ). Subsequent studies revealed deficits in social functioning ( 5 – 7 , 32 ); for example, younger age at onset was associated with worse long-term adaptive behaviors, independent of neurologic disability, as evaluated by the Adaptive Behavior Assessment System ( 7 ). Blum et al administered the Patient-Reported Outcomes Measurement Information System Psychosocial Impact Illness questionnaire to patients with NMDARE ( 6 ).…”

“…Part 1 assessed demographics, clinical features, and long-term outcomes; part 2 assessed QOL. Part 1 collected data on (1) age, (2) sex, (3) onset date, (4) presence of associated tumors, (5) neurological status and outcomes, as determined by the modified Rankin Scale (mRS) score (15), (6) intensive care unit (ICU) stays, (7) the need for mechanical ventilation, (8) presence of neuropsychiatric sequelae or personality changes, (9) return to previous work or school, (10) presence of any disability or handicap affecting daily life at home, and (11) presence of clinical relapses. Detailed questionnaire information is included in the Supplementary Methods.…”

“…Most patients with NMDARE generally respond well to immunotherapy and achieve neurologically favorable outcomes ( 3 ). However, in contrast to the substantial motor recovery demonstrated by these patients, adverse sequelae—including cognitive ( 4 ), sleep ( 5 ), and psychosocial disorders ( 6 , 7 )—often persist many years post-disease onset ( 8 ). In addition, pediatric patients with NMDARE often demonstrate fatigue, potentially worsening quality of life (QOL) ( 9 ).…”

N2 Year in Review

“…Regarding anti-NMDA receptor encephalitis (NMDARe), 2 studies assessed the prognosis of this disease in the young- and late-onset patients. 12,13 In an article published in September 2022, Yeshokumar et al 12 performed an analysis of cross-sectional informant-reported data of 41 patients/caregivers of patients with NMDARe treated at 3 major academic hospitals. Neurologic disability was assessed with the modified Rankin Scale (mRS) and functional outcomes with the Adaptive Behavior Assessment System, 3rd edition (ABAS-3).…”