Anti-NMDA receptor encephalitis recovery persists up to 3 years after diagnosis

Key takeaways:

• Cognitive recovery was greatest within the first 6 months of diagnosis, persisting up to 36 months.
• After the 36 months, 30% of participants did not resume school or work, and 18% who did required adjustments.

Many individuals diagnosed with anti-NMDA receptor encephalitis continued to have cognitive issues — particularly with memory and language — up to 3 years after diagnosis, according to a recent study.

In addition, participants often faced challenges surrounding social functioning, energy and overall well-being.

“As opposed to the often rapid recovery of neurologic symptoms of anti-[NMDA receptor] encephalitis such as seizures and movement disorders, the recovery of cognitive deficits is believed to take months to years,” Juliette Brenner, MD, neurology resident and doctoral candidate in the department of neurology at Erasmus MC University Medical Center in Rotterdam, the Netherlands, and colleagues wrote in Neurology.

Brenner and colleagues conducted a cross-sectional, prospective cohort study of 92 individuals aged 16 years and older (mean age, 29±2 years; 77% women) in the Netherlands who were diagnosed with anti-NMDA receptor encephalitis before July 2023.

All participants exercised independence prior to their illness and participated in a comprehensive cognitive battery encompassing four domains: memory; language; perception and construction; and attention and executive functions. The researchers established functional outcomes by combining participants’ modified Rankin Scale [mRS] score and return-to-work/educational status.

Patient-reported outcome measures (PROMs) were based on a review of existing encephalitis literature, which included the Short Form Health Survey II, WHO Disability Assessment Schedule, Fatigue Severity Scale, Beck Depression Inventory, Hospital Anxiety and Depression Scale, 5-Level 5-Dimension EuroQoL and WHO-5 Well Being Index. All testing metrics were completed online.

Brenner and colleagues compared outcomes with references and between groups based on clinical characteristics and functional outcomes. These included T-tests for normalized data and nonparametric tests for patient-reported data. Recovery was quantified by plotting outcomes against time-of-assessment.

The researchers then engaged in multiple follow-up visits with study participants who fit within a 2-year post-diagnosis window, leaving at least a 6-month gap between rounds of assessments.

Overall, 85 participants completed the cognitive testing and 87 completed the PROMs, with 12 engaging in the prospective follow ups.

According to the results, the largest improvements in cognitive scores occurred within the first 6 months, and improvements were demonstrated up to 36 months post-diagnosis.

However, Brenner and colleagues found that, after the 36-month window, 34% of participants recorded persistent impairment and 65% scored below average in one or more cognitive domains, despite a “favorable” outcome measured by mRS (2 or less) in the majority (91%). Data showed the most affected domains were memory and language.

Regarding the PROMs, chief complaints among study participants were emotional well-being, social functioning, energy levels and quality of life.

In addition, the researchers noted that 30% of participants did not resume regular school or work, and 18% who did required adjustments. The main issues with resumption of school or work centered on processing speed and overall well-being.

“There is a need for standardized, sensitive outcome assessments in anti-NMDAR encephalitis and for extended and comprehensive rehabilitation,” Brenner and colleagues wrote.