Long-term brain changes in NMDA receptor encephalitis

Researchers from Charité – Universitätsmedizin Berlin have gained new insights into the long-term effects of NMDA receptor encephalitis. In this section, first author Dr. Stephan Krohn and senior author and ECN PI Prof. Carsten Finke answer questions about their research findings.

What was the research question or scientific inquiry behind your study?

NMDA receptor encephalitis has only been discovered in 2007. It belongs to a group of autoimmune conditions in which the immune system attacks the body’s own brain. The disease primarily affects younger women and manifests with a combination of severe neurological and psychiatric symptoms. Although acute symptoms often respond well to immunosuppressive treatment, many patients experience substantial morbidity for years after disease onset. However, the brain changes that underlie this long-term morbidity remain largely unclear.

^{MRI of the healthy human brain. In patients with NMDA receptor encephalitis, such images often appear unremarkable. In contrast, complexity analysis detects subtle changes that are not discernible by visual inspection alone. © Charité | Stephan Krohn}

How did you approach the topic?

In this study, we investigated the clinical course of 70 patients with NMDA receptor encephalitis. To this end, we characterized their acute symptoms at disease onset as well as persistent symptoms after immunotherapy in a later disease stage. Additionally, we analyzed brain MRI recordings and compared the brains of patients and healthy control participants. For this, we used fractal dimensionality, a recent neuroimaging measure that quantifies the brain’s morphological complexity. Moreover, we applied a statistical technique that captures how much the brain of an individual patient deviates from a reference of healthy brains.

What did you discover?

About two-thirds of patients showed persistent symptoms after immunotherapy, most commonly memory dysfunction and psychiatric symptoms. Additionally, our MRI analyses revealed subtle structural brain changes in patients compared with controls. These changes were associated with long-term clinical outcomes: Patients with persistent symptoms showed markedly stronger brain changes than patients without persistent symptoms. This relationship was observed both for persistent memory dysfunction and for persistent psychiatric symptoms.

Was there anything that surprised you?

Almost all patients experienced psychiatric symptoms in the acute phase, and about one-third continued to show psychiatric symptoms after treatment. A surprising observation was how clearly these symptoms shifted over time: While the acute phase was marked by psychotic symptoms like delusions and hallucinations, affective symptoms such as depressivity or emotional lability were predominant in the post-acute phase.

What’s your takeaway?

Our study shows that post-acute outcomes of NMDA receptor encephalitis are linked to long-term changes in brain structure. Moreover, our work highlights the importance of persistent memory dysfunction and psychiatric symptoms as an obstacle to long-term recovery. Not least, complexity analysis of structural MRI data represents a promising new approach to detect subtle brain changes. We are currently exploring this framework in other diseases as well.

Source

Krohn et al. Structural brain changes and clinical outcomes of patients with NMDA receptor encephalitis in Germany: a cross-sectional study. Lancet Psychiatry 2026 Aug 13. doi: 10.1016/S2215-0366(26)00191-4

Original Publication

Charité – Universitätsmedizin Berlin

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