A rapidly progressive neurological syndrome with ataxic and parkinsonian features in a patient with small-cell lung cancer and serum NFH/NFM reactivity: a case report

Paraneoplastic neurological syndromes are immune-mediated disorders associated with malignancy, whereas paraneoplastic parkinsonism is rare and may be misdiagnosed as idiopathic or atypical parkinsonism. The clinical significance of serum anti-neurofilament heavy chain (NFH) and anti-neurofilament medium chain (NFM) antibodies remains incompletely understood. We report a woman in her late 60s with rapidly progressive parkinsonism who underwent clinical evaluation, serum and cerebrospinal fluid antibody testing, neuroimaging, lung biopsy, treatment, and follow-up assessment. Results: The patient presented with gait instability, bradykinesia, rigidity, poor levodopa response, cerebellar ataxia, dysarthria, occasional choking, cognitive impairment, and behavioral abnormalities. Serum tissue-based assay showed weak, nonspecific cerebellar immunoreactivity and was interpreted as inconclusive. Cell-based assays detected serum NFH and NFM reactivity at titers of 1:100, whereas cerebrospinal fluid testing was negative. Chest CT revealed a right lower lobe mass, and lung biopsy confirmed limited-stage small-cell lung cancer. After corticosteroids, cyclophosphamide, and antitumor therapy, her neurological symptoms improved markedly, with the MDS-UPDRS Part III score decreasing from 55 to 21. Paraneoplastic parkinsonism should be considered in patients with subacute or rapidly progressive atypical parkinsonism, especially when levodopa response is poor and additional bulbar, cerebellar, or neuropsychiatric features are present. Serum NFH/NFM antibodies may provide a tumor-associated neuroimmunological clue, although their pathogenic significance remains uncertain.