Clinical approach to neurological paraneoplastic syndromes

Neurological paraneoplastic syndromes are immune-mediated disorders. The diagnosis of paraneoplastic syndromes is often difficult because they are rare and the onset of symptoms usually precedes detection of the underlying malignancy. Accurate diagnosis depends on recognition of the clinical phenotypes likely to be associated with a paraneoplastic aetiology and detection of an anti-neuronal antibody. Clinical phenotypes associated with a high risk of a paraneoplastic cause are limbic encephalitis, encephalomyelitis, rapidly progressive cerebellar syndrome, opsoclonus-myoclonus syndrome, subacute sensory neuronopathy, enteric neuropathy and Lambert Eaton myasthenic syndrome. Clinical phenotypes with an intermediate risk of a paraneoplastic aetiology are brainstem encephalitis, myelopathy, stiff person syndrome, Morvan syndrome and retinopathy. Anti-neuronal antibodies are extremely useful in the diagnosis of paraneoplastic neurological syndromes, but false-negative results can occur when only serum or cerebrospinal fluid (CSF) is tested. Commercial antibody panels do not include all antibodies associated with paraneoplastic syndromes, and if this diagnosis is strongly suspected, serum and CSF should be sent to a research laboratory. The risk of a false-positive result is increased if antibody tests are requested when there is a low pre-test probability of a paraneoplastic syndrome or if an antibody is detected in low titre.