Late-onset anti-NMDA receptor encephalitis.
OBJECTIVE
To describe the clinical features and outcome of anti-NMDA receptor (NMDAR) encephalitis in patients ≥45 years old.


METHODS
Observational cohort study.


RESULTS
In a cohort of 661 patients with anti-NMDAR encephalitis, we identified 31 patients ≥45 years old. Compared with younger adults (18-44 years), older patients were more often male (45% vs. 12%, p < 0.0001), had lower frequency of tumors (23% vs. 51%, p = 0.002; rarely teratomas), had longer median time to diagnosis (8 vs 4 weeks, p = 0.009) and treatment (7 vs. 4 weeks, p = 0.039), and had less favorable outcome (modified Rankin Scale score 0-2 at 2 years, 60% vs. 80%, p < 0.026). In multivariable analysis, younger age (odds ratio [OR] 0.15, confidence interval [CI] 0.05-0.39, p = 0.0001), early treatment (OR 0.60, CI 0.47-0.78, p < 0.0001), no need for intensive care (OR 0.09, CI 0.04-0.22, p < 0.0001), and longer follow-up (p < 0.0001) were associated with good outcome. Rituximab and cyclophosphamide were effective when first-line immunotherapies failed (OR 2.93, CI 1.10-7.76, p = 0.031). Overall, 60% of patients older than 45 years had full or substantial recovery at 24 months follow-up.


CONCLUSIONS
Anti-NMDAR encephalitis is less severe in patients ≥45 years old than in young adults, but the outcome is poorer in older patients. In this age group, delays in diagnosis and treatment are more frequent than in younger patients. The frequency of underlying tumors is low, but if present they are usually carcinomas instead of teratomas in younger patients. Early and aggressive immunotherapy will likely improve the clinical outcome.
From the Department of Neurology (M.J.T., I.G., M.R.R., F.G., J.D.), Hospital Clinic, Universitat de Barcelona/Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Spain; Department of Neurology and Neurosciences (M.J.T., L.M., M.R.R., R.B.-G., J.D.), Perelman School of Medicine, Hospital of the University of Pennsylvania, Philadelphia; Department of Neurology (T.I.), Kitasato University School of Medicine, Sagamihara; Department of Neurology (I.K.), Brain Research Institute, Niigata University, Japan; Department of Neurology (L.B.), Hospital Universitario La Fe, Valencia; Biostatistics and Data Management Platform (A.T.), IDIBAPS, Hospital Clinic; and Institució Catalana de Recerca i Estudis Avançats (ICREA) (J.D.), Barcelona, Spain.
Maarten J
MJ
Titulaer
Lindsey
L
McCracken
Iñigo
I
Gabilondo
Takahiro
T
Iizuka
Izumi
I
Kawachi
L
L
Bataller
A
A
Torrents
Myrna R
MR
Rosenfeld
Rita
R
Balice-Gordon
Francesc
F
Graus
Josep
J
Dalmau
D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D060426:Anti-N-Methyl-D-Aspartate Receptor Encephalitis / Q000188:drug therapy* / Q000378:metabolism; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008297:Male; D008875:Middle Aged; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D000069283:Rituximab; D016896:Treatment Outcome; D055815:Young Adult
D058846:Antibodies, Monoclonal, Murine-Derived; D016194:Receptors, N-Methyl-D-Aspartate; D000069283:Rituximab