Objective: To report a rare case of autoimmune Parkinsonism associated with anti-recoverin antibodies, highlighting atypical presentation , diagnostic challenges and immunotherapy response.

Background: Parkinsonism is traditionally viewed as a neurodegenerative disorder, but growing evidence suggests immune-mediated mechanisms .Anti-recoverin antibodies, classically associated with paraneoplastic retinopathy, have recently been implicated in CNS autoimmunity.

Method: A 57-year-old male presented with 4 months history of progressive bradykinesia, resting tremors, postural instability along with daytime somnolence, apathy, and cognitive decline (memory deficits, speech changes). He had childhood-onset refractory focal seizures managed with antiseizure medication,diabetes and hypertension. On examination, he exhibited masked facies, hypophonic speech, impaired vertical gaze, symmetrical rigidity, bradykinesia, and resting/postural tremors (MDS-UPDRS: 40).

Neuroimaging & CSF: MRI revealed mild cerebral and cerebellar atrophy without midbrain or basal ganglia involvement; CSF showed elevated protein (70 mg/dL) with mild pleocytosis (3 WBCs).

Autoimmune Workup: Anti-recoverin was strongly positive (3+); PET-CT was normal.

A trial of high-dose Syndopa (levodopa-carbidopa) produced no improvement, effectively ruling out idiopathic Parkinson’s disease and supporting an immune-mediated etiology. Differential diagnoses, including PSP-C, drug-induced parkinsonism, and neurogenetic storage disorders, were considered but excluded.

Treatment & Response:

He was treated with IV methylprednisolone (1g for 5 days) followed by oral steroids. Incidentally, he tested positive for hepatitis core antibody and was given entecavir. Subsequently, he received two doses (1g each) of rituximab 2 weeks apart.

Results: MDS-UPDRS improved from 40 to 10, reaching 5 at 3 months.

Conclusion: This is the first reported case of anti-recoverin-associated autoimmune parkinsonism with PSP-like phenotype. Previously, autoimmune parkinsonism has been described in association with IgLON5, anti-CV2, anti-amphiphysin, and anti-Ma antibodies, but anti-recoverin has rarely been implicated【1,2,3,4】.The dramatic response to immunotherapy underscores the need for early screening and treatment .How many treatable cases are slipping through the cracks? It’s time to rethink Parkinsonism, challenge outdated assumptions, and embrace neuroimmunology as the game-changer it is.

MRI sequences

References: 1. Kitazaki Y, Shirafuji N, Takaku N, et al. Autoimmune basal ganglia encephalitis associated with anti-recoverin antibodies: A case report. eNeurologicalSci. 2021;25:100382. Published 2021 Nov 24. doi:10.1016/j.ensci.2021.100382
2. Gaig C, Graus F, Compta Y, et al. Clinical manifestations of the anti-IgLON5 disease. Neurology. 2017;88(18):1736-1743.
3. Gomathy SB, Saikrishna K, Radhakrishnan DM, et al. Atypical Parkinsonism with Positive Anti-amphiphysin Antibodies: Expanding the Phenotypic Spectrum. Ann Indian Acad Neurol. 2024;27(2):201-203.
4. Dalmau J, Graus F, Villarejo A, et al. Clinical analysis of anti-Ma2-associated encephalitis. Brain. 2004;127(Pt 8):1831-1844.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/beyond-neurodegeneration-anti-recoverin-autoantibodies-in-immune-mediated-parkinsonism/