Late-onset anti–NMDA receptor encephalitis

Abstract

Objective: To describe the clinical features and outcome of anti-NMDA receptor (NMDAR) encephalitis in patients $45 years old.Method: 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 5 0.002; rarely teratomas), had longer median time to diagnosis (8 vs 4 weeks, p 5 0.009) and treatment (7 vs 4 weeks, p 5 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] 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. Anti-NMDA receptor (NMDAR) encephalitis is an autoimmune disorder that usually affects children and young adults, resulting in severe neuropsychiatric symptoms that often respond to treatment. [1][2][3][4] Experience with older patients is limited to a single case report 5 and series comprising patients of all ages, but no further information is available. We report a detailed clinical analysis of 31 patients $45 years old and describe several novel features associated with this age group.METHODS Patients with immunoglobulin G antibodies against the NR1 subunit of NMDAR were identified from a series of 661 cases with anti-NMDAR encephalitis.2 Detailed information on patients $45 years old, either as individual cases or age group, has not been reported previously. We used 45 years as the cutoff age because a similar threshold has been used in other autoimmune neurologic disorders, like myasthenia gravis. Clinical information was obtained by the authors or referring physicians at the acute stage of the disease.2 Follow-up information was obtained at regular intervals after symptom onset; neurologic status was assessed with the modified Rankin Scale (mRS) score. 6 Initial treatment was considered a failure if no sustained improvement occurred within 4 weeks after initiation of immunotherapy or tumor removal, and if the mRS score remained $4.2 Serum and CSF antibody studies were conducted as reported. Demographic information and symptoms were analyzed with the Fisher exact test, Fisher-Freeman-Halton test, or Mann-Whitney U test when appropriate, comparing these 31 patients with 338 recently reported patients (aged 18-44 years).

Recognizing Autoimmune-Mediated Encephalitis in the Differential Diagnosis of Limbic Disorders

“…27 In patients older than 45 years, the outcome was reportedly favorable, whereas 23% of patients had underlying carcinomas instead of teratomas. 32 Despite this ominous clinical presentation, approximately 50% of patients respond to first-line immunotherapies, often with full remission, whereas patients who do not respond to treatment or who experience relapse should be reassessed for the presence of an underlying contralateral or recurrent teratoma.…”

Management of Immune-Mediated Paraneoplastic Neurological Disorders

“…Mortality, often caused by intensive care complications, is about 7-9 %. Of all anti-NMDAR encephalitis cases, 38 % are paraneoplastic and associated in young women, very rarely in men, with teratomas, and in patients > 45 years with carcinomas [41]. The occurrence of teratomas increases among adolescents and is at 15 % in female patients < 14 years, at 30 % < 18 years and at 60 % > 18 years [39].…”

Anti-NMDA-reseptorencefalitt

“…Den rammer i stor grad unge kvinner (> 80 %), men også menn og barn (1,2). Kjønnsfordelingen ser derimot ut til å vaere nokså jevn hos pasienter over 45 år (3). Pasientene har typisk fravaer av tidligere psykiatrisk sykehistorie.…”