{
  "abstract": "Background Immune checkpoint inhibitors (ICIs) have become a widespread clinical strategy due to their favorable outcomes and improved tolerance compared to conventional cytotoxic therapies. However, neurologic immune-related adverse events (irAE-Ns) are rare complications of ICI therapy that can lead to permanent neurologic deficits and potentially death. These irAE-Ns can either arise through de novo induction of an anti-neurological immune response or through unmasking of a latent paraneoplastic process. Current literature does not differentiate pure iatrogenic encephalitis from paraneoplastic encephalitis, despite potentially having different prognoses. We sought to compare how pure iatrogenic and combined iatrogenic/paraneoplastic cases of ICI-induced forms of encephalitis differ in response to immunosuppression and overall outcomes, assessing patterns in patient prognosis and treatment response.Methods Articles searched through the PubMed database spanned from 2011 (first authorization of ICIs by the FDA) to May 2025. Inclusion criteria included patients diagnosed with encephalitis or encephalitis-related conditions with an ICI-related etiology. We defined each case of encephalitis based on the 2021 Paraneoplastic Neurologic Syndrome (PNS) Care Score, using clinical phenotype, antibody type, presence of a high-risk cancer for paraneoplastic syndromes, and time of follow-up. 1Patients scored as definite or probable were marked as iatrogenic/paraneoplastic, and those scored as possible/non-PNS were marked as purely iatrogenic. The patients’ response to ICI discontinuation, corticosteroids, and/or other immunomodulation were recorded. Treatment response was designated as complete if symptoms resolved, partial if some improvement occurred, stable if symptoms neither improved nor worsened, and progressive if symptoms worsened. Differences in response rates were calculated using a χ2 test.Results We conducted a systematic review of 105 articles documenting cases of immune checkpoint inhibitor-induced encephalitis and encephalitis-related conditions. A total of 238 patients were included (123 men [51.7%]; median age, 63.0 years). 162 of those patients (68%) were characterized with pure iatrogenic ICI-induced encephalitis and 76 (32%) were determined to be iatrogenic/paraneoplastic. 45.4% received anti-PD1 therapy, 31.1% received anti-PDL1 therapy, 18.5% received combination therapy, and 5.0% received anti-CTLA4 therapy. Patients with an iatrogenic etiology experienced significantly more favorable neurologic responses to therapy (complete or partial response) compared to patients with an iatrogenic/paraneoplastic etiology (80% vs 51%, P = 0.0001).Conclusions Accurate diagnosis of PNS is essential in the context of ICIs, as they can induce two distinctive patterns of encephalitis: pure iatrogenic with a favorable prognosis or paraneoplastic with a guarded prognosis. Clinicians should apply the PNS score to patients with ICI-induced irAE-Ns for proper prognostication.Reference Graus F, Vogrig A, Muñiz-Castrillo S, et al. Updated diagnostic criteria for paraneoplastic neurologic syndromes. Neurol Neuroimmunol Neuroinflammation. 2021;8(4):e1014. Published 2021 May 18. doi:10.1212/NXI.0000000000001014",
  "authors": [
    {
      "affiliations": [
        "Case Western Reserve University School of Medicine, Cleveland, OH, USA"
      ],
      "name": "Claire Yin"
    },
    {
      "affiliations": [
        "University Hospitals Cleveland Medical Center, Cleveland, OH, USA"
      ],
      "name": "Davina N Patel"
    },
    {
      "affiliations": [
        "University Hospitals Cleveland Medical Center, Cleveland, OH, USA"
      ],
      "name": "Rohit R Rao"
    },
    {
      "affiliations": [
        "University Hospitals Cleveland Medical Center, Cleveland, OH, USA"
      ],
      "name": "Talal M Alumri"
    },
    {
      "affiliations": [
        "University Hospitals Cleveland Medical Center, Cleveland, OH, USA"
      ],
      "name": "Hesham Abboud"
    }
  ],
  "title": "405 Differentiating outcomes of pure iatrogenic encephalitis from paraneoplastic encephalitis in ICI-treated patients",
  "uid": "4275c035-99f8-5f62-a4ca-c1a6db911a4b"
}