Atypical Presentation of Pembrolizumab-related Meningoencephalitis With Neutrophilic Pleocytosis in Advanced Non-small Cell Lung Cancer
Priya Reddy1, Peyton Murin2, Karthik Narayanan2, Mehnaz Afsheen2, Daniel Weber2, Deniz Atilgan2, Jared Cohen3, Mercier Philippe4, Kenneth Smithson2, Philip Sun2
1Saint Louis University, 2Department of Neurology, 3Department of Internal Medicine, 4Department of Surgery, Saint Louis University
Background:
Reported cases of non-infectious encephalitis with immune checkpoint inhibitor (ICI) use typically involve lymphocytic pleocytosis. We describe a rare case involving neutrophilic pleocytosis in a patient recently switched on ICI therapy to pembrolizumab.
Results:
A 77-year-old male, baseline neuro-intact, was diagnosed with metastatic squamous non-small cell carcinoma of the lung in 2024 (program death ligand-1 90%). In September 2025, he had a local recurrence despite carboplatin and lung radiation. Brain imaging showed intra-axial, cerebellar enhancing lesions concerning for metastasis. Due to durvalumab intolerability, his regimen was changed to pembrolizumab monotherapy. In October, he presented to our ED for several days of confusion with associated mild hyponatreamia. CT head revealed moderate communicating hydrocephalus and transependymal edema. His mentation continued to decline, leading to intubation on hospital day (HD) 5. MRI on HD 6 showed worsening of the communicating hydrocephalus and diffuse basal leptomeningeal enhancement with nodularity, requiring an emergent extraventricular drain placement. These MRI findings were new since his previous MRI brain prior to pembrolizumab initiation. Cerebrospinal fluid (CSF) studies were significant for neutrophil-predominant pleocytosis (90% of the total 29 white blood cells/mm3), elevated protein of 48mg/dl, hypoglycorrhachia (glucose 17mg/dl), and undetected malignant cells. CSF infectious workup was negative. He later developed multiple episodes of synchronous twitching movements in the right upper extremity with associated lateral neck flexion. Continuous electroencephalogram demonstrated left parietal epileptiform discharges with focal slowing. For suspected pembrolizumab-associated encephalitis, he was empirically started on high-dose methylprednisolone 1mg/kg/d. Antibody Prevalence in Epilepsy and Encephalopathy (APE2) score was 7.
Conclusions:
This case highlights a probable neurological immune-related adverse event, with a unique finding of neutrophilic pleocytosis, which occurred within a month of combination therapy with durvalumab transitioned to pembrolizumab monotherapy. Rigorous multidisciplinary evaluations should involve diagnostic elucidation while ruling out alternative causes, for which immunosuppressive therapy may be harmful.
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.