Case Presentation: A 61-year-old woman with no pertinent past medical history presented to the hospital with two months of progressive numbness that began with her left foot and hands and eventually extended to her forearms. She developed clumsiness in her hands, gait unsteadiness, and had a 20-pound weight loss. A CT scan of the chest on arrival showed lymphadenopathy and a tumor concerning for primary malignancy in the right upper lobe. She underwent a bronchoscopy with lymph node biopsy that showed high grade large cell neuroendocrine carcinoma. Her serum was sent for paraneoplastic antibody testing and was positive for anti-ANNA1/anti-Hu antibodies. She underwent 7 cycles of carboplatin/etoposide systemic chemotherapy. Her tumor was highly responsive to chemotherapy, and she was found to be in remission on PET-CT after completion. She initially had mild improvement in her neurologic symptoms while on a high-dose prednisone taper. However, several months into cancer treatment she developed acute onset of an unusual and devastating constellation of symptoms including significantly worsened coordination, neuropathy, uncontrollable arm flailing, diplopia, unilateral hearing loss, urinary frequency, shallow breathing, muscular fasciculations and labile blood pressures concerning for autonomic dysfunction. She was unable to stand on her own and required help with all activities of daily living, despite being cancer-free. In an attempt to reverse her rapidly worsening symptoms, she was admitted for IV steroids and plasmapheresis. Unfortunately, there was no significant improvement in her neurological exam, and she was discharged to a SNF for physical therapy. At a follow up visit, she reported that with physical therapy she had regained the ability to feed herself but remained otherwise disabled.
Discussion: Paraneoplastic neurologic syndromes are potentially devastating sequelae of cancers caused by an immunologic response directed against shared antigens expressed by the cancer and the nervous system. Classical paraneoplastic antibodies, such as the Hu antibody (ANNA-1), are directed against intracellular neuronal proteins, and their detection almost always indicates the presence of an underlying tumor. Anti-Hu paraneoplastic antibody syndrome typically presents with encephalomyelitis, cerebellar degeneration, sensory neuronopathy, and autonomic dysfunction. It is associated with small cell lung cancer predominantly, though it can be found in other cancers.There are two general approaches to treatment of paraneoplastic syndromes: removing the antigen source by treating the underlying tumor and suppressing the immune response with therapies such as steroids, plasma exchange, IVIG, or rituximab. Classical paraneoplastic syndromes that target intracellular antigens, such as anti-Hu, typically do not respond well to treatment and physicians can often only stabilize the symptoms at best, as seen in our patient.
Conclusions: This case demonstrates the tragic consequences of paraneoplastic neurologic syndromes. Despite successful treatment of the lung cancer with chemotherapy, our patient continued to have major neurologic decline. Immune modulation with high dose steroids and plasma exchange were ineffective. We present this case in hopes that hospitalists will recognize the signs and symptoms of paraneoplastic neurologic syndromes early enough to attempt stabilization before it is too late.