A 66-year-old man comes to the emergency department due to dizziness, dysarthria, and bilateral limb ataxia. His symptoms have been steadily worsening over the last 2 weeks. He has no other medical problems and takes no medications. He has a 50-pack-year smoking history and does not use alcohol or illicit drugs. Chest x-ray shows a mass in his right lung. He is admitted to the hospital for evaluation, but his neurologic symptoms continue to progress. He dies several months later despite receiving appropriate treatment. Autopsy shows extensive cerebellar Purkinje cell degeneration. Which of the following best describes the etiology of this patient's neurologic condition?

Question

A 66-year-old man comes to the emergency department due to dizziness, dysarthria, and bilateral limb ataxia.  His symptoms have been steadily worsening over the last 2 weeks.  He has no other medical problems and takes no medications.  He has a 50-pack-year smoking history and does not use alcohol or illicit drugs.  Chest x-ray shows a mass in his right lung.  He is admitted to the hospital for evaluation, but his neurologic symptoms continue to progress.  He dies several months later despite receiving appropriate treatment.  Autopsy shows extensive cerebellar Purkinje cell degeneration.  Which of the following best describes the etiology of this patient's neurologic condition?

Quizplus · Accepted Answer

11ec160b_39b3_845b_9249_99447e1714bb_MD0001_00 This patient's lung mass, cerebellar symptoms, and autopsy findings are consistent with paraneoplastic cerebellar degeneration. This paraneoplastic syndrome is most commonly associated with small cell lung cancer as well as breast, ovarian, and uterine malignancies. Patients exhibit progressively worsening dizziness, limb and truncal ataxia, dysarthria, and visual disturbances (eg, diplopia, oscillopsia). Paraneoplastic cerebellar degeneration is due to an immune response against tumor cells that cross-reacts with Purkinje neuron antigens, leading to acute-onset rapid degeneration of the cerebellum. Anti-Yo, anti-P/Q, and anti-Hu are the most common antibodies detected in the serum. Antibodies are not always detectable; thus, paraneoplastic cerebellar degeneration is diagnosed clinically after excluding other conditions. (Choice B) Some paraneoplastic syndromes occur due to the production of hormone-like substances from tumor cells, but these would not cause the neurological findings described in this case. (Choice C) Acute cerebellitis (post-viral cerebellar ataxia) occurs most often in children 2-3 weeks following varicella, measles, or Epstein-Barr virus infection. It presents with cerebellar symptoms (eg, ataxia, nystagmus, dysarthria) that usually resolve completely within 3 weeks. (Choice D) Cerebellar metastasis can cause progressively worsening subacute cerebellar symptoms. Additional findings such as headaches or decreased consciousness are often present due to significant mass effect from the tumor. However, autopsy would show metastatic cancer cells with surrounding inflammation as opposed to Purkinje cell degeneration. (Choice E) Adverse effects from systemic chemotherapy can include a wide range of neurologic complications. However, this patient's symptoms began before the lung mass was identified and his autopsy findings are more specific for subacute cerebellar degeneration. (Choice F) Cerebellar infarction presents with vertigo, nystagmus, ipsilateral limb ataxia, and truncal lateropulsion (falling toward the lesion). Although repeated vascular events could result in a stepwise progressive loss in neurologic function, this process would most likely occur over several years and affect multiple vascular territories throughout the brain (causing a wide range of neurologic deficits). Autopsy would show areas of liquefactive necrosis (acute infarcts) and glial scarring (chronic infarcts). Educational objective: Paraneoplastic syndromes can occur due to the production of hormone-like substances from tumor cells. They can also result from immune reactions against tumor cells that cross-react with normal cells, causing dysfunction and/or damage to healthy organs and tissues. Neurologic paraneoplastic syndromes (eg, paraneoplastic cerebellar degeneration) are an autoimmune phenomenon. __________ References: Small-cell lung cancer, paraneoplastic cerebellar degeneration and the Lambert-Eaton myasthenic syndrome (http://www.ncbi.nlm.nih.gov/pubmed/9278623)

A 66-Year-Old Man Comes to the Emergency Department Due to Dizziness