B80-6-34 Brain on Fire: Pembrolizumab Induced Cerebellitis

Immune checkpoint inhibitors (ICIs) have transformed cancer therapy but can cause immune-related adverse events (irAEs) affecting multiple organs. Neurological irAEs are uncommon (<1%) and range from mild headache to severe autoimmune encephalitis and Guillain-Barré syndrome. Pembrolizumab, an anti-PD-1 antibody, has been associated with immune-mediated encephalitis in < 0.2% of cases. Cerebellitis secondary to ICIs remains exceptionally rare and poorly characterized. We present the case of a 67-year-old male with medical history of hypothyroidism and bladder carcinoma who presented with four weeks of progressive headache, slurred speech, nausea, diplopia, severe ataxia, and unsteadiness. He had completed eight months of pembrolizumab therapy for bladder carcinoma, which had been on hold pending cystoscopy evaluation. On examination, he was alert, afebrile, and hemodynamically stable. Neurological evaluation revealed scanning dysarthria, bilateral dysmetria, dysdiadochokinesia, and horizontal and vertical nystagmus without focal weakness.Routine metabolic and infectious workups were unremarkable. Cerebrospinal fluid analysis showed lymphocytic pleocytosis (WBC 33, 100% mononuclear) and elevated protein (64.8 mg/dL). Initial brain MRI was negative for T2-FLAIR hyperintense lesions. Immunological panels were negative for anti-Hu, anti-Yo, and anti-Ri antibodies but positive for VGCC antibodies (>30 pmol/L), suggestive of non-paraneoplastic cerebellar degeneration. With a strong suspicion for inflammatory etiology patient was treated with methylprednisolone (1 gm IV daily for five days). The headache and nausea resolved, the dysmetria and nystagmus slightly improved, though truncal ataxia persisted. Due to clinical deterioration IVIG’s therapy was initiated, and the patient was transferred to the ICU. Unfortunately, he developed aspiration pneumonia that acutely compromised the clinical scenario and passed away. Immune checkpoint inhibitors induced cerebellitis is rare but clinically significant, often misdiagnosed as stroke, intoxication, or metabolic dysfunction. The delayed onset of neurological irAEs highlights the need for ongoing vigilance even after immunotherapy cessation. Early recognition and prompt initiation of corticosteroids or immunomodulatory therapy may improve outcomes, though evidence remains limited. Pembrolizumab-induced cerebellitis is a rare but potentially fatal complication. Clinicians should maintain high suspicion for cerebellar dysfunction in patients receiving ICIs, as early identification and treatment are crucial to prevent irreversible neurological injury.