Anti-NMDAR Encephalitis: How Long Does Cognitive Recovery Take After Diagnosis?

Cognitive recovery from anti-NMDA receptor (anti-NMDAR) encephalitis may continue up to 36 months after diagnosis, with cognitive deficits, especially in domains of memory and language, persisting for years after encephalitis. These are the findings of a study published in Neurology.

Researchers of a large-scale cross-sectional and prospective study aimed to understand the cognitive recovery trajectory, patient-reported outcomes and related clinical factors, and the association between long-term cognitive outcomes and self-reported quality of life in patients with anti-NMDAR encephalitis.

Eligible participants were enrolled in the Erasmus University Medical Center and were diagnosed with anti-NMDAR encephalitis before July 2023. All patients were aged at least 16 years, had functional independence, and the ability to participate in cognitive tests. Scores on the Glasgow Coma Scale (CGS) were used to determine level of consciousness/responsiveness. Participants who were within 2 years of an anti-NMDAR diagnosis were considered for enrollment in the prospective part of the study.

The researchers collected clinical data from participants’ first or last disease episode. They used 7 patient-reported outcome measures (PROMs) for the analysis:

• the 36-Item Short-Form Health Survey II (SF-36-II),
• World Health Organization Disability Assessment Schedule (WHO-DASII),
• Fatigue Severity Scale (FSS),
• Beck Depression Inventory (BDI),
• Hospital Anxiety and Depression Scale (HADS),
• 5-Level 5-Dimension EuroQoL (EQ-5D-5L), and
• World Health Organization-5 Well-being Index (WHO-5).

Neuropsychologic assessments included a cognitive battery test consisting of 4 cognitive domains — memory, language, perception and construction, and attention and executive function.

A total of 92 patients (mean age at disease onset, 29 years; women, 77%) with anti-NMDAR encephalitis were included, of whom 85 participated in the cognitive tests, 87 in the PROMs, and 12 in the prospective analysis. Neuropsychologic assessments were conducted at a mean of 5 years after encephalitis diagnosis.

The researchers noted an increase in cognitive ability over time, with a sharp increase in the first 6 months and a gradual increase at 36 months (R=0.35; P =.022). Results of the prospective analysis were consistent with these results.

Patients with a recent diagnosis of anti-RMDAR encephalitis (<6 months) had below-average scores in domains of processing, working memory and attention, and perception and construction. At 6 to 18 months after diagnosis, participants had improved scores in all domains, with below-average scores in verbal and working memory and attention, and language. After 36 months, none of the participants had below-average scores in any subdomains, with cognitive recovery remaining steady.

After 36 months, 34% had an impairment in 1 or more cognitive domains, especially memory and language (P =.25 and P =.23, respectively), with 65% having below-average scores.

The researchers noted statistically significant self-reported sequelae in social functioning, energy levels, emotional well-being, depression symptoms, and quality of life beyond 36 months (P <.004, P <.004, P =.026, P =.010, and P <.003, respectively).

Overall, 91% of patients had long-term favorable outcomes, as observed on the mRS, which signified independence in daily activities. However, one-third of participants did not resume occupational activities, such as work or education. Those who resumed vs did not resume occupational activities had better scores on the cognitive tests in processing speed (P =.039).

Overall, the researchers noted, “There is a need for standardized, sensitive outcome assessments in anti-NMDAR encephalitis and for extended and comprehensive rehabilitation.”

Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of the authors’ disclosures.