From the Guidelines
Neuroendocrine tumor-associated encephalitis should be evaluated with a comprehensive panel of autoantibodies, particularly anti-neuronal antibodies, in both serum and cerebrospinal fluid for optimal sensitivity, as recommended by the most recent guidelines 1. The most important serological tests include anti-Hu (ANNA-1), anti-Yo (PCA-1), anti-Ri (ANNA-2), anti-CV2/CRMP5, anti-Ma2/Ta, anti-amphiphysin, and anti-NMDA receptor antibodies. Additional testing should include:
- anti-GAD65
- anti-LGI1
- anti-CASPR2
- anti-GABA-B receptor antibodies The presence of these antibodies can confirm paraneoplastic encephalitis associated with neuroendocrine tumors, particularly small cell lung cancer, pancreatic neuroendocrine tumors, or carcinoid tumors. Testing should be performed before immunotherapy is initiated when possible, as treatment may reduce antibody titers, as noted in the management of encephalitis guidelines 1. Patients with suspected neuroendocrine tumor-associated encephalitis should also undergo comprehensive tumor screening with whole-body imaging (CT, MRI, or PET scans) even if initial serological tests are negative, as antibody-negative paraneoplastic syndromes can occur, and early identification of the underlying neuroendocrine tumor is crucial, as treating the primary tumor often helps resolve the neurological symptoms, as discussed in the context of encephalitis diagnosis and management 1.
Key considerations in the diagnosis and management of neuroendocrine tumor-associated encephalitis include:
- The importance of clinical correlation in interpreting CSF findings and autoantibody results
- The need for a comprehensive diagnostic approach, including neuroimaging, CSF analysis, and serological testing
- The potential for antibody-negative paraneoplastic syndromes and the importance of whole-body imaging in identifying underlying neuroendocrine tumors
- The role of immunotherapy in the management of autoimmune encephalitis and the potential impact of treatment on antibody titers.
From the Research
Neuroendocrine Tumor Serology for Encephalitis
- Neuroendocrine tumors can be associated with paraneoplastic neurological syndromes, including encephalitis, as seen in a case of anti-Hu brainstem encephalitis associated with a pancreatic neuroendocrine tumor 2.
- Anti-Hu antibodies are highly correlated with neurological syndromes when present concomitantly with a neoplasm, and are often associated with small cell lung cancer, but can also be associated with other types of cancer, including neuroendocrine tumors 2.
- Another type of paraneoplastic neurological syndrome is anti-Ma2-associated encephalitis, which is characterized by isolated or combined limbic, diencephalic, or brainstem dysfunction, and is often associated with testicular germ cell tumors or other types of cancer 3.
- The diagnosis of encephalitis typically involves lumbar puncture and cerebrospinal fluid examination, as well as imaging and electroencephalography, and treatment may involve immunotherapy and/or tumor treatment 4, 5.
- Autoimmune encephalitis, including paraneoplastic limbic encephalitis and anti-N-methyl-D-aspartate receptor encephalitis, is an increasingly recognized cause of encephalitis, and may be associated with neuroendocrine tumors or other types of cancer 6, 5.
- The clinical presentation of encephalitis can vary widely, and may include symptoms such as fever, seizures, altered consciousness, and psychiatric manifestations, and treatment is often supportive, with specific treatment available for certain types of infections or autoimmune disorders 4, 5.