Painless, Symmetric, Ascending Weakness and Sensory Loss

A 60-year-old man sought care for painless, symmetric, ascending weakness and sensory loss affecting the lower, greater than upper, extremities, progressing over 3 weeks with associated orthostatism. He was diffusely areflexic and had symmetric weakness, distal greater than proximal, with normal bulbar strength. Muscle atrophy was not appreciated, and fasciculations were absent. Sensory examination revealed pan-sensory loss at the feet and hands. His gait was unsteady with prominent steppage. He was unable to climb stairs, kneel, or arise without assistance. Pertinent medical and social history included a spinal fusion at C5-T1, a 10-pack-year smoking history, and congestive heart failure, New York Heart Association class III with an intracardiac defibrillator for ventricular fibrillation, and taking carvedilol and furosemide. Needle electromyography and nerve conduction studies showed a severe axonal sensory-motor polyneuropathy with proximal involvement, suggesting polyradicular colocalization. Cerebrospinal fluid obtained during unremarkable spinal myelography, for exclusion of spinal compression, showed normal and abnormal findings: total nucleated cells, 3/µL; glucose, 87 mg/dL; and protein, 326 mg/dL. Sural nerve biopsy showed marked active axonal injury without significant inflammatory infiltrates. Expanded autoimmune neuroimmunologic testing by indirect immunofluorescence staining identified the classic pattern for antineuronal nuclear antibody type 1 –immunoglobulin G. Chest radiography and computed tomography showed a consolidation and volume loss in the left lower lobe without identifiable mass. The patient was diagnosed with paraneoplastic axonal sensory-motor polyneuropathy in the setting of antineuronal nuclear antibody type 1-immunoglobulin G positivity and likely small cell lung carcinoma. Acute motor axonal neuropathy was thought to be the diagnosis, and the patient was treated with plasma exchange. He continued to worsen and was transferred to the intensive care unit with new shortness of breath. Escalated therapy with intravenous immunoglobulin did not help. He had development of urinary retention, bulbar weakness, confusion, and flail limbs in all extremities. On identification of antineuronal nuclear antibody type 1-immunoglobulin G, he was treated with intravenous methylprednisolone, but his condition worsened. The patient and his family opted for comfort measures. His defibrillator was turned off, and he died 20 days after first coming to the hospital. At autopsy, small cell lung carcinoma of the left lung was identified without bronchial mass or metastasis. Neural tissues had diffuse microglial activation, with scattered microglial nodules and prominent perivascular chronic lymphocytic infiltrates. Antineuronal nuclear antibody type 1-immunoglobulin G autoimmunity was first reported in 1965. Patients had sensory neuropathy with nonmetastatic cancer and dorsal ganglia degeneration at autopsy. Neuropathy is the most common neurologic presentation, but the neurologic phenotypes have expanded since the original descriptions to include cerebellar, cognitive, and spinal cord involvement.