Paraneoplastic syndromes: overview

Paraneoplastic neurological syndromes are immune-mediated disorders of the nervous system which occur in the setting of malignancy but are not related to direct malignant infiltration, metastatic deposits, metabolic or nutritional disorders, or adverse effects of therapy. The pathogenesis of paraneoplastic neurological syndromes is not fully understood. Cancer cells may express antigens which mimic neuronal epitopes, leading to the formation of self-reactive T cells and B cells. While there are several well-recognised syndromes associated with specific paraneoplastic antibodies and specific malignancies, it is not clear for all of these disorders whether the antibody is pathogenic (i.e. directly implicated in neuronal damage).

There are several recognised ‘classical’ paraneoplastic syndromes which should raise clinical suspicion for an underlying malignancy. However, many people presenting with these syndromes will not have underlying malignancy, and many people with an underlying malignancy may present with ‘non-classical’ neurology. Similarly, ‘paraneoplastic’ antibodies can be detected in well people without malignancy or neuronalogical disease. As neither clinical findings nor serology are 100% sensitive and specific, the diagnosis of a paraneoplastic neurological syndrome relies on a constellation of supportive clinical findings, with or without demonstration of an antibody, exclusion of other causes, and pursuit of the underlying malignancy.

Here are non-exhaustive lists of well-characterised paraneoplastic antibodies and classical paraneoplastic syndromes. Adapted from this great review.

Antibody associations with specific paraneoplastic syndromes:

Antibody Features Malignancies
Anti-Hu Encephalomyelitis

Limbic encephalitis

Sensory neuronopathy

Sensorimotor neuropathy

Lung cancer (85% Small Cell)


Prostate cancer

Anti-Yo Paraneoplastic cerebellar degeneration Ovarian cancer

Breast cancer

Anti-CRMP2 Encephalomyelitis

Limbic encephalitis


Optic neuritis

Paraneoplastic cerebellar degeneration

Small cell lung cancer


Anti-Ma Limbic encephalitis Testicular cancer
Anti-Ri Opsoclonus-myoclonus syndrome

Paraneoplastic cerebellar degeneration

Jaw dystonia


Breast cancer

Small cell lung cancer

Anti-recoverin Retinopathy Small cell lung cancer

Classic paraneoplastic syndromes and their cognate antibodies:

Syndrome Associated antibodies
Subacute cerebellar degeneration Hu, Yo, CRMP5, Ri, Tr, Amphiphysin, VGCC
Encephalomyelitis Hu, CRMP5, Amphiphysin
Limbic encephalitis Hu, Ma, CRMP5, Ri, Amphiphysin, NMDAR, Lgi1, CASPR2, GABAb, AMPAR, mGluR5, GlyR, GAD
Opsoclonus-myoclonus Ri, Hu, Ma, NMDAR
Retinopathy Hu, CRMP5, Recoverin
Stiff person syndrome Amphiphysin, GlyR, GAD
Anti-amphiphysin Stiff person syndrome
Subacute sensory neuronopathy Hu, CRMP5, Amphiphysin
Chronic intestinal pseudoobstruction Hu, CRMP5, Amphiphysin
Dermatomyositis Mi2, Jo1, SRP