Perelman School of Medicine at the University of Pennsylvania

Center for Autoimmune Neurology


Diseases of this type were first described in patients with known cancer, and given the description ‘paraneoplastic’.  However, a deeper understanding of the science found that these diseases can also occur in patients without cancer.  Additionally, identification of the pathogenic antibodies on a cellular level has led to a reclassification and renaming of many of these diseases.  Paraneoplastic is still sometimes used to describe these diseases, but we now tend to describe these diseases as antibody mediated neurologic diseases.   They are typically named according to the area of nervous system that is affected, the type of immune response, and/or the type of symptoms.  For example, the most common disease we study is "Anti-NMDAR encephalitis".  Where the prefix 'anti' refers to an autoimmune response against 'NMDA receptors' in the brain, which causes 'encephalitis' or swelling resulting in a disruption of normal brain signaling. 

The diseases below can be classified according to the patient’s specific set of symptoms or syndrome (see tabs to the left), or can be described using characteristics of the antigen on a cellular level (as is common in scientific literature).  The chart below also lists the most commonly associated cancers for each disease, but it important to keep in mind not all patients will have cancer.

Predominant Syndrome
Type of Antigen
Associated Cancer
NMDAR Characteristic syndrome (see here) Synaptic cell surface Ovarian teratoma, Carcinomas
AMPAR Limbic encephalitis Synaptic cell surface Lung, Breast, Thymoma
GABAbR Limbic encephalitis Synaptic cell surface Lung, Neuroendocrine
LGI1 Limbic encephalitis, Faciobracial dystonic seizures Synaptic cell surface Thymoma


Encephalitis, Morvan Syndrome, Acquired neuromyotonia Axonal cell surface Thymoma
mGluR1 Paraneoplastic Cerebellar Degeneration Synaptic cell surface Hodgkin's lymphoma
mGluR5 Limbic encephalitis Synaptic cell surface Hodgkin's lymphoma
DPP6 / DPPX Encephalitis with nervous sytem and GI hyper-excitability Synaptic cell surface None
GABAaR Encephalitis with prominent seizures / status epilepticus Synaptic cell surface Infrequent
GAD65 Stiff-person syndrome, seizures, type 1 diabetes, encephalitis Intracellular synaptic Usually none
GlyR Stiff-person syndrome, PERM Synaptic cell surface Infrequent
DNER (previous Tr) Paraneoplastic Cerebellar Degeneration Cell surface  Hodgkin's lymphoma (high risk)
Yo (PCA-1) Paraneoplastic Cerebellar Degeneration Intracellular

Ovary, Breast, Gynecologic

Amphiphysin Stiff-person syndrome, encephalomyelitis, Paraneoplastic Cerebellar Degeneration Intracellular synaptic Breast, small cell lung cancer
Zic4 Paraneoplastic Cerebellar Degeneration Synaptic cell surface Small cell lung cancer
VGCC LEMS, Paraneoplastic Cerebellar Degeneration Synaptic cell surface Small cell lung cancer, lymphoma
Hu (ANNA-1) Encephalomyelitis, Paraneoplastic Cerebellar Degeneration, Sensory-predominant neuronopathy Intracellular Small cell lung cancer, other
Ri (ANNA-2) Paraneoplastic Cerebellar Degeneration, Brainstem encephalitis, opsoclonus-myoclonus Intracellular Breast, gynecological, small cell lung cancer
CV2/CRMP5 Encephalomyelitis, Paraneoplastic Cerebellar Degeneration, Chorea, Peripheral neuropathy Intracellular synaptic Small cell lung cancer, thymoma, other
Ma proteins Limbic encephalitis, hypothalamic, brainstem encephalitis, Paraneoplastic Cerebellar Degeneration (infrequently) Intracellular Testes, lung, other
D2R Basal ganglia encephalitis Synaptic cell surface Infrequent
Iglon5 Sleep disorder, Neurodegeneration Cell surface None