Abstract Details

Title Clinical and Paraclinical Features Distinguishing Paraneoplastic from Immune Checkpoint Inhibitor-induced Encephalitis

Topic Autoimmune Neurology

Presentation(s) P6 - Poster Session 6 (5:00 PM-6:00 PM)

Poster/Presentation
Number 2-008

Objective To characterize clinical and paraclinical differences between pnEncephalitis and irEncephalitis to facilitate diagnosis and inform management.

Background Encephalitis can occur as a paraneoplastic syndrome (pnEncephalitis) or as a neurologic immune-related adverse event following immune checkpoint inhibitor therapy (irEncephalitis). Clinical differentiation between these cancer-associated encephalitides remains challenging.

Design/Methods From a prospective outpatient tertiary cohort (2006–2022), we retrospectively identified patients meeting criteria for pnEncephalitis or irEncephalitis and compared clinical presentations, paraclinical findings, and outcomes using nonparametric methods.

Results

From the cohort (N=340), 26 patients with pnEncephalitis and 11 with irEncephalitis were identified. Common malignancies included ovarian teratoma (29.7%), lung cancer (18.9%), and Hodgkin's lymphoma (5.4%). In irEncephalitis patients, encephalitis developed a median of 22 days after ICI initiation.

Clinical presentations including memory deficits, focal neurologic deficits, fever, and altered mental status were similar between groups (p>0.05). Seizures were more common in pnEncephalitis (65.4% vs 18.2%, p=0.02).

MRI abnormalities occurred in both groups (42.3% vs 72.7%, p=0.18). Vascular or dural involvement was exclusive to irEncephalitis (0% vs 50%, p=0.02), including leptomeningeal enhancement, multifocal white matter hyperintensities, and chronic microvascular changes. Hippocampal and limbic involvement was primarily observed in pnEncephalitis (54.5% vs 12.5%, p=0.15). CSF parameters were similar (p>0.05): WBC, protein, IgG index, and oligoclonal bands.

Nearly all received corticosteroids (92.3% vs 100%, p=1.0); plasmapheresis was used more frequently in pnEncephalitis (57.7% vs 9.1%, p=0.01). IVIG, rituximab, and cyclophosphamide use was similar. Readmission and mortality rates were comparable.

Conclusions Despite similar clinical presentations, distinct paraclinical differences distinguish irEncephalitis from pnEncephalitis. Limbic system involvement and higher seizure rates characterize pnEncephalitis, consistent with the epileptogenic nature of these regions, while vascular/dural abnormalities are exclusive to irEncephalitis. These patterns suggest distinct immunopathological mechanisms that may guide diagnosis and treatment selection.

Authors/Disclosures
Sophia Zhao, BA, BS PRESENTER	Miss Zhao has nothing to disclose.
Jordan Benderoth	Miss Benderoth has nothing to disclose.
Ralph Habis, MD (Johns Hopkins School of Medicine)	Dr. Habis has nothing to disclose.
Roba El-Zibaoui, MD	Dr. El-Zibaoui has nothing to disclose.
Arun Venkatesan, MD, PhD (Johns Hopkins Hospital)	Dr. Venkatesan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen Pharmaceuticals. The institution of Dr. Venkatesan has received research support from NIH. The institution of Dr. Venkatesan has received research support from U.S. DOD.
John Probasco, MD, FAAN (The Johns Hopkins Hospital)	Dr. Probasco has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for NEJM Clinician. The institution of Dr. Probasco has received research support from Roche/Genentech.

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