Paraneoplastic Neurological
Disorders

Paraneoplastic neurological disorders (PNDs) are rare syndromes that are caused by, or associated with, an underlying neoplasm. PNDs do not occur by direct tumor involvement in neuroanatomic tissues;¹ it is believed that most are caused by an immune response against onconeural antigens.² These antigens, common to both neoplastic and normal neural tissue, are recognized as foreign and lead to autoantibodies attacking both the tumor as well as portions of the nervous system.³

This autoantibody response leads to progressive neurological damage.² PNDs can affect many parts of the nervous system and, unlike most gradual neurodegenerative disorders, PNDs typically exhibit rapid onset of symptoms: "Patients may develop a severe neurologic syndrome over the course of hours, although more frequently over the course of days to weeks."⁴

PNDs are diagnostically challenging for two reasons. First, at the onset of the neurological symptoms, an individual's cancer has usually not been discovered.³ PNDs can precede the detection of a tumor by months or years.⁵ Second, other neurological disorders can mimic paraneoplastic syndromes.³ These symptoms are "relatively common to the neurologist: for example, sensory neuropathy, idiopathic cerebellar dysfunction, obscure visual complaints."⁴

Despite these challenges, in most instances, the presence of paraneoplastic antibodies establishes that the disorder is paraneoplastic.³ In addition, many autoantibodies are usually associated with specific tumors.² The presence of a specific autoantibody can therefore help indicate the most likely underlying tumor. "The detection of antibodies against onconeuronal antigens points to the diagnosis of a paraneoplastic syndrome and focuses the search for an underlying tumor to a few organs."⁶

The table below outlines the most well-known paraneoplastic autoantibodies, the clinical presentations associated with them, and their most commonly associated cancers.

Table3
Autoantibody		Clinical Presentation		Commonly Associated Cancer(s)
Anti-Hu		Encephalomyelitis, sensory neuronopathy		Small Cell Lung Cancer (SCLC) and neuroblastoma
Anti-Ma		Cerebellar dysfunction, brainstem dysfunction		Breast, lung, colon7
Anti-Ta		Limbic encephalitis, brainstem dysfunction		Testicular
Anti-Yo		Cerebellar degeneration		Gynecologic, breast
Anti-Ri		Cerebellar ataxia, opsoclonus		Breast, gynecologic, SCLC
Anti-CAR		Photoreceptor degeneration		SCLC and others
Anti-VGCC		Lambert-Eaton myasthenic syndrome		SCLC

Learn More about Paraneoplastic Neurological Disorders.

Download the Clinical Presentation Chart.

1. Brown, R.H. PARANEOPLASTIC NEUROLOGICAL SYNDROMES. In Harrison's Principles of Internal Medicine, ed. A.S. Fauci et al., 622-627. 1998. McGraw-Hill: New York.
2. Dalmau, J.O. and Posner, J.B. Paraneoplastic syndromes affecting the nervous system. Seminars in Oncology 1997; 24(3): 318-328.
3. Dalmau, J.O. and Posner, J.B. Paraneoplastic Syndromes. Archives of Neurology 1999; 56:405-408.
4. Darnell, R.B. PARANEOPLASTIC SYNDROMES. In Current Diagnosis in Neurology, ed. E. Feldmann, 137-141. 1994. St. Louis: Mosby-Year Book, Inc.
5. Brown, R.H. PARANEOPLASTIC NEUROLOGICAL SYNDROMES. In Harrison's Principles of Internal Medicine, ed. A.S. Fauci et al., 622-627. 1998. McGraw-Hill: New York.
6. Voltz, R. A SEROLOGIC MARKER OF PARANEOPLASTIC LIMBIC AND BRAIN-STEM ENCEPHALITIS IN PATIENTS WITH TESTICULAR CANCER. The New England Journal of Medicine 1999; 340:1788-1795.
7. Dalmau, J., et al., Ma1, a novel neuron- and testis-specific protein, is recognized by the serum of patients with paraneoplastic neurological disorders. Brain 1999; 122:27-39.