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Comment
. 2025 Oct;43(2):636-644.
doi: 10.1007/s12028-025-02287-0. Epub 2025 May 29.

Clinical Description and Acute Outcomes of Cryptogenic Encephalitis in the Intensive Care Unit

Jackson A Roberts #  1   2 , Mohamed Ridha #  3   4 , Carla Y Kim  5 , Yifei Sun  6   7   8 , Elizabeth Carroll  4 , Jan Claassen  4 , Kiran T Thakur  5   4
Affiliations
Comment

Clinical Description and Acute Outcomes of Cryptogenic Encephalitis in the Intensive Care Unit

Jackson A Roberts et al. Neurocrit Care. 2025 Oct.

Abstract

Background: Prognosis of acute encephalitis is variable and dependent on the underlying etiology, early treatment, and clinical course. Despite extensive evaluation, a cause of acute encephalitis may not be discovered, presenting a challenge to clinicians when discussing prognosis with families. We sought to determine whether clinical and radiographic features may discriminate short-term outcomes in patients with severe cryptogenic encephalitis.

Methods: We performed a single-center, retrospective study of patients admitted with cryptogenic encephalitis (i.e., unknown etiology at time of discharge) to the Columbia University Irving Medical Center neurologic intensive care unit (ICU) and the Morgan Stanley Children's Hospital ICU from 2010 to 2020. A favorable discharge outcome was defined as Glasgow Outcome Scale score greater than or equal to 4. Using multivariable logistic regression modeling, we analyzed clinical and radiographic variables associated with favorable short-term outcome.

Results: Among 204 total patients with encephalitis admitted to the ICU, 51.0% were classified as cryptogenic. The median age was 49.9 (interquartile range 31-64) years, and the most common presenting symptoms were altered mental status (74.0%), fever (56.7%), and headache (46.2%). Favorable outcome occurred in 63.5% of cryptogenic cases. In the fully adjusted model, age above 50 years (odds ratio [OR] 0.30, 95% confidence interval [CI] 0.11-0.81; p = 0.017), active malignancy (OR 0.07, 95% CI 0.01-0.63; p = 0.018), and intubation (OR 0.20, 95% CI 0.07-0.55, p = 0.002) were associated with reduced odds of favorable outcome. Older age, active malignancy, and intubation were identified as predictors of lower Glasgow Outcome Scale score using ordinal logistic regression.

Conclusions: Clinical characteristics may aid early prognostication of cryptogenic encephalitis. Further mechanistic study of the association between active malignancy among patients with cryptogenic encephalitis is warranted.

Keywords: Encephalitis; Intensive care units; Neurocritical care; Neuroinflammatory diseases; Prognosis.

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Conflict of interest statement

Declarations. Conflicts of interest: The authors declare no conflicts of interest. Ethical approval/informed consent: We have adhered to standard ethical guidelines in the preparation of this work. This study has institutional review board approval from the Columbia University Irving Medical Center Institutional Review Board (AAU6908). This type of study does not require formal consent.

Comment on

  • Cryptogenic Encephalitis: The New Abnormal.
    Risso C, Sonneville R. Risso C, et al. Neurocrit Care. 2025 Oct;43(2):378-381. doi: 10.1007/s12028-025-02289-y. Epub 2025 May 29. Neurocrit Care. 2025. PMID: 40442428 No abstract available.

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