Danish study finds cognitive problems may persist years after autoimmune encephalitis

A new nationwide Danish study suggests the standard outcome measure (the usual measures for health) after AE is missing long-term cognitive damage.

Background

On paper, most people who survive autoimmune encephalitis (AE) are recorded as having made a good recovery. But a new Danish study suggests that record is incomplete.

Researchers led by Thomas Agerbo Gaist at Odense University Hospital assessed 86 of 108 eligible adults diagnosed with AE in Denmark between 2009 and 2022, a median of more than six years after symptom onset.

Because Denmark tests for these antibodies centrally, the team could reach almost everyone who had ever been diagnosed, rather than only those still attending a specialist clinic.

Reassuring at first

On the modified Rankin Scale (mRS), results appeared reassuring: every patient with NMDA receptor (NMDAR) encephalitis and 86% of those with limbic encephalitis had scores indicating a good functional outcome (day-to-day functioning).

Then the neuropsychologist sat down with them, and the story changed.

Around 45% of the patients with NMDAR and 43% of the patients with limbic encephalitis had deficits across multiple cognitive domains, particularly memory and executive function. Around 15% of people without prior herpes encephalitis met criteria for post-encephalitis dementia. Fatigue affected roughly a third, and both fatigue and low mood correlated closely with how satisfied patients felt with life overall.

The dementia finding was worth noting. It was more likely in people who had been more severely ill, who were older when they became ill, and who had relapsed. All twelve were men.

The problem with numbers

The authors note these figures depend heavily on how the data are analysed. A second, more conservative method dropped multidomain impairment across the whole cohort from 43% to 25% and more than doubled the proportion with no deficits at all, from 19% to 44%.

The MoCA test

Of the bedside screening tools compared, the test known as ‘MoCA’, which stands for the Montreal Cognitive Assessment, performed best. In limbic encephalitis it picked up around 80% of those with deficits. However, it still missed a substantial proportion of people, detecting only 56% for NMDAR encephalitis.

A caveat on the study itself: it captured people at a single moment rather than following them over time, and those who didn’t take part had been more severely ill. That means these results might paint a more optimistic picture than the reality for everyone diagnosed with AE.

The researchers

The full list of researchers is Thomas Agerbo Gaist, Lisbeth Rosenlund Lodahl, Henrik Akre Thorup, Mette Scheller Nissen, Klaus Hansen, Thomas Harbo, Sophia Rekers, Carsten Finke, and Morten Blaabjerg.

One of the researchers, Carsten Finke, is a member of Encephalitis International’s Scientific Advisory Panel, which provides expert professional guidance, and informs the organisation’s research strategy, information resources and guidance. Carsten Finke is Heisenberg Professor for Cognitive Neurology and Consultant Neurologist at the Department of Neurology at Charité Berlin.

Conclusion

The practical takeaway is clear: the MoCA test used in this study matches best with neuropsychological performance and is recommended by the researchers as the bedside test of choice if a neuropsychologist is not readily available.

Referral for full neuropsychological assessment remains the best way to detect cognitive problems long after acute AE.

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To view the original paper, click here.

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For our information on cognitive changes after encephalitis, click here.