Cancer Therapy-Induced Encephalitis

Abstract

Encephalitis associated with cancer therapies is a rare but serious complication that can significantly impact patients' quality of life and it requires prompt identification and management. Over the past two decades, immunotherapy-particularly immune checkpoint inhibitors-has become a cornerstone of cancer treatment, with up to half of metastatic cancer patients in economically developed countries now receiving these therapies. The widespread adoption of immunotherapy has led to improved survival rates and long-term remissions, even in patients with advanced metastatic disease. However, as immune modulators, these therapies can trigger a range of immune-related adverse events, including a variety of novel neurological toxicities. Among these, encephalitis is of particular concern due to its potential severity, which can compromise treatment outcomes. This review aims to provide a comprehensive overview of the literature on this condition, highlighting optimal diagnostic strategies and management approaches to mitigate the risk of significant morbidity, while also comparing encephalitis induced by immunotherapy with that caused by traditional chemotherapies and targeted oncologic treatments.

Keywords: BiTE; CAR-T; ICANS; adverse event; autoimmune; cancer; checkpoint inhibitor; encephalitis; immunotherapy; neurotoxicity.

Figure 1

Diagnosis of ICI-induced encephalitis. (A) Early symptoms, especially confusion, must raise suspicion of encephalitis. (B) Differential diagnosis to be evoked; (C) workup to be done. ¹ Metabolic panel: electrolytes, glucose, creatinine, bilirubin, liver enzymes, ammonia, arterial blood gas analysis, vitamins B1 and B12, thyroid function tests, basal cortisol concentration, ANCA; ² autoantibody panel: autoantibodies: AGNA (SOX1), AMPAR1/2, Amphiphysin, CRMP5 (CV2), DPPX, GABAR, GAD65, Hu (ANNA1), Ma1, Ma2, Ri (ANNA2), TG, TPO, TR, VGKC (anti-LGI1, anti-CASPR2), Yo (PCA1), ZIC44; Paraneoplastic antibodies: NMDAR, AMPAR1/2, VGKC (anti-LGI1, anti-CASPR2), Gly, GABAR. Abbreviations: ANCA = antineutrophil cytoplasmic antibody; CRP = C-reactive protein; CSF = cerebrospinal fluid, EEG = electroencephalogram > HSV-1 = herpes simplex virus type 1; HSV-2 = herpes simplex virus type 2, MRI = magnetic resonance imaging; PCR = polymerase chain reaction; SS = sedimentation speed; VZV = varicella-zoster virus. Adapted from [37].