Background <p>Immune checkpoint inhibitor (ICI) therapy unleashes the body’s natural immune system to fight cancer. Neurological immune-related adverse events (NirAEs) are rare but can be severe.</p> Case presentation <p>In this report, we present a 47-year-old man of Han ethnicity who was diagnosed with lung adenocarcinoma with intracranial metastasis. Initially, the patient underwent intracranial radiotherapy followed by first-line and maintenance chemotherapy with pemetrexed, cisplatin and bevacizumab, and a partial response was achieved without significant toxicity. After progression, the patient received second-line chemotherapy with carboplatin and albumin-bound paclitaxel as well as an ICI, sintilimab, every 28&#xa0;days. After completing nine cycles of sintilimab therapy, the patient suddenly experienced lower limb paresthesia, weakness and temporary confusion. Findings from diagnostic studies, including laboratory, electrophysiological and imaging studies, combined with the clinical presentation led to the diagnosis of NirAEs, including peripheral neuropathy and demyelination of the central nervous system. Sintilimab therapy was suspended, and intravenous corticosteroid therapy was initiated, resulting in a temporary rapid resolution of all neuropathic symptoms. However, the patient died within one month after the onset of neuropathic symptoms.</p> Conclusion <p>This extremely rare case of NirAEs affecting both the peripheral and central nervous systems had the worst prognosis.</p>