Longitudinal clinical outcomes, cognitive impairment, and mood symptoms in anti-NMDAR encephalitis
Annalisa Morgan1, Yadi Li2, Nicolas Thompson2, Alexander Rae-Grant3, Justin Abbatemarco4, Vineet Punia5, Stephen Hantus5, Rachel Galioto4, Amy Kunchok4
1Cleveland Clinic- Neurological Institute, 2Cleveland Clinic- Quantitative Health Sciences, Lerner Research Institute, 3Cleveland Clinic- Lerner College of Medicine, 4Cleveland Clinic- Mellen Center, 5Cleveland Clinic- Charles Shor Epilepsy Center
Objective:
To characterize longitudinal outcomes in anti-NMDA receptor (anti-NMDAR) encephalitis.
Background:

Outcomes in anti-NMDAR encephalitis are poorly understood but may be influenced by factors not adequately captured using the modified Rankin Scale (mRS).

Design/Methods:

This retrospective, observational cohort study examined outcome measures (mRS and clinical assessment scale in autoimmune encephalitis, CASE) in adults with anti-NMDAR-IgG in CSF at hospital discharge and long-term follow-up. Linear and logistic regression modeled outcomes. Mixed models examined predictor effects by time. Subgroups with evaluations for cognitive impairment (CI) (Montreal Cognitive Assessment or Mini-Mental State Examination) >6 months from symptom onset and depression (Patient Health Questionnaire-9) and anxiety (General Anxiety Disorder-7) within 1 year of long-term follow-up were reported. Spearman correlations were examined between mood and final CASE scores.

Results:

Thirty-eight patients (76.3% female, median disease onset age=28 years, IQR=22-36) were included. The majority received first- (97.4%) and second-line (68.4%) immunosuppressants at a median of 3.9 weeks (IQR=2.1-9.7).

 

Median/mean mRS and CASE were 4 (IQR=3-5) and 12.7 (SD=7) at baseline and 2 (IQR=1-3) and 4 (SD=4.1) at long-term follow-up (median=70 weeks, IQR=51-174). Both improved from baseline (p<0.001).

 

At hospital discharge (median=10 weeks, IQR=6-17), predictors of higher CASE and mRS scores included: dysautonomia, coma/lethargy, seizures/status epilepticus, and intensive care unit admission (p<0.05).

 

At long-term follow-up, only onset weakness predicted higher mRS scores (OR=5.62, CI 1.02-30.90, p=0.047). Seizures were uncommon (3%). Psychiatric morbidity was the main contributor to final CASE scores (mean=1.3, SD=0.94).

 

In subgroup analyses, moderate-severe CI (50%), depression (29.5%), and anxiety (41.6%) were frequent. There was a correlation between depression (r=0.65, p<0.01) and anxiety (r=0.79, p<0.01) measures with final CASE memory sub-scores.

Conclusions:
Different clinical factors predict early versus long-term outcomes in anti-NMDAR encephalitis. Only onset weakness predicts long-term disability by mRS. Long-term CI and mood symptoms were frequently noted. Highlighting a complex interplay, mood symptoms correlated with CASE memory sub-scores.
10.1212/WNL.0000000000202839