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Paraneoplastic syndromes: when to suspect, how to confirm, and how to manage

Neurological manifestations of cancer are common, disabling, and often multifactorial (table 1). The concept that malignant disease can cause damage to the nervous system above and beyond that caused by direct or metastatic infiltration is familiar to all clinicians looking after cancer patients. These “remote effects” or paraneoplastic manifestations of cancer include metabolic and endocrine syndromes such as hypercalcaemia, and the syndrome of inappropriate ADH (antidiuretic hormone) secretion. Paraneoplastic neurological disorders (PNDs) are remote effects of systemic malignancies that affect the nervous system. The term PND is reserved for those disorders that are caused by an autoimmune response directed against antigens common to the tumour and nerve cells.

View this table:

 Table 1 
Neurological manifestations of malignant disease



PNDs are much less common than direct, metastatic, and treatment related complications of cancer, but are nevertheless important because they cause severe neurological morbidity and mortality and frequently present to the neurologist in a patient without a known malignancy. Because of the relative rarity of PND, neurological dysfunction should only be regarded as paraneoplastic if a particular neoplasm associates with a remote but specific effect on the nervous system more frequently than would be expected by chance . For example, subacute cerebellar ataxia in the setting of ovarian cancer is sufficiently characteristic to be called paraneoplastic cerebellar degeneration, as long as other causes have been ruled out. However, carpal tunnel syndrome in a patient with cancer is not paraneoplastic because both are reasonably common conditions which may co-exist in the same patient.

There have only been a few studies addressing the incidence and prevalence of PND in the overall cancer population. A number of studies have focused on either certain cancers typically associated with PND—for example, small cell lung cancer (SCLC)1—or on specific anti-neuronal antibodies and their neurological and tumour associations.

The incidence of PND …