Parkinsonism as a Potential Neurologic Immune-Mediated Adverse Event of Immune Checkpoint Inhibitors.
Parkinsonism as a Potential Neurologic Immune-Mediated Adverse Event of Immune Checkpoint Inhibitors.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Lyon, FR · Author affiliation
French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Hopital Neurologique, Bron, France.Location evidence
Bron, FR · Author affiliation
French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Hopital Neurologique, Bron, France.Location evidence
Salpêtrière, FR · Author affiliation
Sorbonne University, INSERM, CIC-2503, Department of Pharmacology, AP-HP Pitié Salpêtrière Hospital, Paris, France.Location evidence
Paris, FR · Author affiliation
Sorbonne University, INSERM, CIC-2503, Department of Pharmacology, AP-HP Pitié Salpêtrière Hospital, Paris, France.Location evidence
FR · Author affiliation · country only
Institut de Cancérologie de l'Ouest, Saint Herblain, France.Location evidence
Nantes, FR · Author affiliation
Centre d'investigations cliniques, INSERM 1413, CHU Nantes, Nantes, France.Location evidence
Montpellier, FR · Author affiliation
Department of Medical Pharmacology and Toxicology, Montpellier University Hospital, France; and.Location evidence
Lille, FR · Author affiliation
Regional Pharmacovigilance Centre of Lille, CHU Lille, France.Location evidence
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Original abstract
OBJECTIVES: Immune checkpoint inhibitor (ICI)-related parkinsonism is an exceedingly rare neurologic immune-related adverse event (irAE). METHODS: We reviewed retrospectively the French Pharmacovigilance Agency and French National Center for Autoimmune Encephalitis and Paraneoplastic Neurologic Syndromes Lyon databases (2015-2025) following identification of index case. RESULTS: We identified 4 male and one female patient, with a median age of 67 years (range 34-75), who developed acute-to-subacute parkinsonism after a median of 4 ICI cycles (range 1-12). The predominant phenotype was bilateral akinetic-rigid syndrome (rigidity n = 5, bradykinesia n = 4, tremor n = 3); the median modified Rankin Scale score at onset was 3. CSF analysis showed pleocytosis in 2/4 tested patients and elevated protein in 4/4 tested patients. Dopamine transporter imaging demonstrated bilateral dopaminergic denervation in both patients tested (n = 2), with documented reversibility in one. ICI discontinuation alone (n = 1/2) or combined with immunomodulatory therapy (n = 3) yielded clinical improvement over a median follow-up of 15 months (range 3-30). Levodopa/carbidopa supplementation was required in 2 patients. DISCUSSION: Post-ICI-related parkinsonism is a rare but potentially reversible irAE. Early recognition and prompt ICI discontinuation may favor significant clinical recovery. Immunosuppressive therapy should be considered for severe cases or those not improving after ICI discontinuation alone.