Abstract Details

Anti-Hu paraneoplastic neurological syndromes (PNS) include movement disorders such as chorea, ataxia, dyskinesia, myoclonus. So far, no cases of parkinsonism have been reported. We describe an anti-Hu subacute paraneoplastic parkinsonism with dysautonomia due to a thymoma.

A 71 year-old female complained of a 2-month history of digestive pseudo-obstruction, dysphagia, urinary symptoms and orthostatic hypotension, complicating an underlying asymmetric extrapyramidal syndrome that had started few months before. Blood tests, MRI, autoimmunity and oncomarkers were negative. Thoracic imaging showed a mediastinal widening, better characterized by needle biopsy as thymoma. Screening for PNS with anti-Hu, Ri, Yo, LGI1, CaspR2, NMDAR, Ma2, CRMP5 and GAD was positive for anti-Hu on both serum and cerebrospinal fluid (CSF). Complete response of dysautonomia to intravenous immunoglobulins (IVIg), followed by thymectomy confirmed the diagnosis of anti-Hu related PNS. Extrapyramidal symptoms partially improved with daily L-dopa during hospitalization, with a 20% reduction in the MDS-UPDRS. However, no further improvement was observed with IVIg+thymectomy+radiotherapy, and the DaT-SPECT 4 months later still showed pathologic asymmetric results. Over 20 months, the patient’s motor function progressively recovered, therefore L-dopa tapering was commenced and completed in three months. MDS-UPDRS and DaT-SPECT one month after drug discontinuation were normal.

Antibody-induced parkinsonism is usually associated to anti-NMDAR, CRMP5, Ri, Ma2, GAD or VGKC, rather than anti-Hu. Our patient’s motor symptoms might have derived from antibody binding to basal ganglia, as supported by their presence in the CSF. Also noteworthy, the evolution of DaT-SPECT over time, possibly due to slow kinetics of antibody release from presynaptic dopaminergic neurons, which could explain persistence of symptoms for months. 

Anti-Hu can produce subacute parkinsonism-dysautonomia whereby parkinsonism is clinically/radiologically asymmetric and partially responsive to L-dopa. Contrary to dysautonomia, complete response to IVIg+tumor therapy is much slower. Primary differential diagnosis is with rapidly progressing multiple system atrophy with predominant parkinsonism.