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) Neuroblastoma Prostate cancer
Anti-Yo	Paraneoplastic cerebellar degeneration	Ovarian cancer Breast cancer
Anti-CRMP2	Encephalomyelitis Limbic encephalitis Polyneuropathy Optic neuritis Paraneoplastic cerebellar degeneration	Small cell lung cancer Thymoma
Anti-Ma	Limbic encephalitis	Testicular cancer
Anti-Ri	Opsoclonus-myoclonus syndrome Paraneoplastic cerebellar degeneration Jaw dystonia Laryngospasm	Breast cancer Small cell lung cancer
Anti-recoverin	Retinopathy	Small cell lung cancer

Classic paraneoplastic syndromes and their cognate antibodies:

Syndrome	Associated antibodies
CNS
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
PNS
Subacute sensory neuronopathy	Hu, CRMP5, Amphiphysin
Chronic intestinal pseudoobstruction	Hu, CRMP5, Amphiphysin
LEMS	VGCC, SOX1
Dermatomyositis	Mi2, Jo1, SRP