Paraneoplastic degeneration of the substantia nigra with dystonia and parkinsonism

Abstract

A 42-year-old woman suffered unexplained weight loss followed by action tremor and difficulty initiating gait. Three months after onset of symptoms, infiltrating ductal carcinoma of the breast, metastatic to liver and lymph nodes, was diagnosed and treated briefly with cyclophosphamide, methotrexate, and 5-flourouracil (5FU). Severe symmetric action and postural tremor with a myoclonic component developed, with minimal rest tremor, severe dysarthria and dysphagia, small-stepped and slightly ataxic gait progressing to a bedbound state, and severe widespread dystonic posturing. The latter began as a typical parkinsonian posture of trunk and upper extremities and progressed to a fixed and painful flexion of the elbows and wrists and extension of fingers and neck. Sinemet, anticholinergics, baclofen, diazepam, and plasmapheresis gave no benefit. The patient died of complications of immobility 5 months after neurologic symptom onset. Autopsy revealed many pigment-laden macrophages in substantia nigra and moderate loss of pigmented neurons. Inflammation, Lewy bodies, and tumor were absent. Cerebellar Purkinje cells were moderately depleted. Mild neuronal loss and gliosis were present in globus pallidus and cerebellar cortex. Stains for anti-human IgG, IgM, kappa, and lambda were negative. This, to our knowledge, is the first report of paraneoplastic degeneration of substantia nigra or paraneoplastic parkinsonism.