Immune‐Related Chorea–Ataxia Induced by <scp>PD</scp> ‐1 Inhibitor (Cemiplimab): A Case Report

Immune checkpoint inhibitors (ICIs) have transformed cancer therapeutics, but their immune-related adverse events (irAEs) increasingly extend beyond classic systemic manifestations to include diverse neurologic syndromes.1 Neurologic irAEs are rare but potentially severe, with autoimmune encephalitis, neuropathies, and myasthenic syndromes being most frequently reported.2, 3 Movement disorders, in contrast, are distinctly uncommon and poorly characterized.4, 5 Here, we describe a patient who developed generalized chorea and truncal ataxia after re-exposure to the programmed cell death-1 (PD-1) inhibitor cemiplimab, highlighting the expanding spectrum of ICI-induced movement disorders. A 72-year-old man with metastatic basaloid cutaneous squamous cell carcinoma was treated with the PD-1 inhibitor cemiplimab. After an initial course, therapy was discontinued due to unrelated clinical considerations. Upon disease progression, cemiplimab was reintroduced. Within weeks of re-exposure, the patient developed involuntary movements involving the face, trunk, and limbs, accompanied by motor impersistence, incoordination, and gait instability. There was no cognitive decline, seizures, or psychiatric symptoms. Neurologic examination revealed generalized chorea with prominent truncal involvement, ataxic gait, and mild dysmetria of the upper limbs. Strength and sensation were preserved. Brain MRI showed no evidence of mass effect, inflammation, or ischemic lesions. Routine blood tests were unremarkable, and infectious workup was negative. Cerebrospinal fluid (CSF) analysis demonstrated markedly elevated protein (186 mg/dL) with normal cell count and negative cytology, consistent with an inflammatory but noninfectious process. No neuronal autoantibodies were detected. Although a tissue-based assay (TBA) was not performed due to limited access to specialized immunohistochemistry in our institution, all commercially available cell-based and immunoblot antibody panels were negative. Given the temporal relationship between cemiplimab re-exposure and symptom onset, along with the inflammatory CSF findings, an immune-related movement disorder secondary to PD-1 blockade was suspected. Cemiplimab was discontinued, and high-dose corticosteroid therapy was initiated with intravenous methylprednisolone 1 g daily for 5 days. The patient experienced gradual improvement, with near-complete resolution of chorea and ataxia over the subsequent weeks. Follow-up video recordings demonstrated striking clinical recovery. This case illustrates a reversible immune-mediated movement disorder induced by a PD-1 inhibitor. While neurologic irAEs occur in approximately 1–5% of patients receiving ICIs,2 movement disorders such as chorea or ataxia remain exceedingly rare.4, 5 Recent literature has strengthened the recognition of cerebellar and movement disorder phenotypes triggered by ICIs, with systematic reviews demonstrating that cerebellar irAEs and immune-mediated movement disorders display heterogeneous presentations, frequently combining ataxia with encephalopathy or hyperkinetic phenomena.8-10 These studies show that mixed phenotypes—such as cerebellitis-plus syndromes or ataxia accompanied by chorea—are increasingly reported, indicating that ICIs may simultaneously affect cerebellar and basal ganglia circuits. The temporal association with drug exposure, absence of structural lesions, inflammatory CSF profile, and steroid responsiveness strongly support an immune-related mechanism.1, 6 Cemiplimab is a fully human monoclonal antibody targeting PD-1, approved for advanced cutaneous squamous cell carcinoma. By enhancing antitumor immune activity, PD-1 blockade may also disrupt self-tolerance, triggering autoreactive T-cell responses against neural antigens.9, 10 The resulting dysfunction can manifest as central nervous system inflammation even in the absence of detectable autoantibodies.7 Although a tissue-based assay was not available for this patient due to local resource limitations, this does not weaken the diagnostic interpretation: recent cohorts show that seronegative presentations are common in cerebellar irAEs, with up to half of patients lacking detectable neuronal antibodies.8-10 Elevated CSF protein without pleocytosis, as observed in this patient, has been described in other ICI-related neurologic syndromes and likely reflects immune-mediated blood–brain barrier dysfunction.2 The phenomenology in our patient—generalized chorea with prominent truncal ataxia (Video 1)—suggests combined basal ganglia and cerebellar involvement. This presentation mirrors recently reported ICI-associated syndromes, in which chorea and ataxia frequently coexist, reinforcing a growing understanding that ICIs can induce multifocal neuroinflammation within motor networks.8-10 Systematic reviews of cerebellar irAEs describe that isolated cerebellitis occurs in only one-third of patients, whereas most cases demonstrate “cerebellitis-plus” involvement, often with movement abnormalities, encephalopathy, or other neurologic features.9, 10 This pattern has been documented in autoimmune chorea associated with systemic autoimmunity and in paraneoplastic contexts,8 reinforcing the overlap between tumor immunity and autoimmunity. The absence of neuronal antibodies in this case does not exclude immune causality, as antibody-negative irAEs are increasingly recognized.7, 9 Prompt recognition and management are critical in ICI-related neurologic syndromes. Discontinuation of the offending agent and initiation of immunosuppression—most commonly corticosteroids—remain the mainstay of treatment.6, 9 The complete recovery observed in this case aligns with previous reports suggesting that early intervention confers favorable outcomes.2, 3 However, recent systematic studies note that relapses and severe courses may occur, particularly in patients with cerebellitis-plus or seropositive phenotypes, emphasizing the importance of close follow-up9,10. In refractory cases, intravenous immunoglobulin, plasmapheresis, or rituximab may be considered.6, 10 This case expands the spectrum of PD-1 inhibitor–associated neurologic irAEs to include chorea–ataxia and underscores the importance of maintaining vigilance for immune-mediated movement disorders in patients receiving checkpoint blockade. By integrating these recent descriptions of ICI-induced cerebellar syndromes and movement disorders, our case further contributes to the evolving recognition of multifocal immune-mediated motor dysfunction associated with PD-1 inhibition. Video documentation is invaluable for objective characterization of phenomenology and for monitoring treatment response. Manuscript Preparation: A. Writing of the first draft, B. Review and Critique. K.A.S.M: 1A G.D.J.P: 1B T.P.F: 1B The authors thank the Neurology and Oncology teams at the Hospital de Amor de Barretos for their clinical support and collaboration. Ethical Compliance Statement: This case was reviewed and approved by the Ethics Committee of the Hospital de Amor de Barretos. Written informed consent was obtained from the patient for publication of this case and accompanying video material. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. Funding Sources and Conflict of Interest: No specific funding was received for this work. The authors declare that there are no conflicts of interest relevant to this work. Financial Disclosures and Conflict of Interest: The authors declare that there are no additional disclosures to report. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.