From the Guidelines
Diagnosing paraneoplastic encephalitis requires a combination of tests, with CSF analysis being the most important test, including cell count and differential, protein, glucose, CSF/serum glucose ratio, albumin quotient, IgG index and synthesis rate, oligoclonal bands, and NAAs panel. The diagnosis of paraneoplastic encephalitis involves a multifaceted approach to detect antibodies, identify underlying malignancies, and evaluate brain abnormalities.
Key Diagnostic Tests
- Blood tests to detect paraneoplastic antibodies such as anti-Hu, anti-Yo, anti-Ri, anti-NMDA receptor, and anti-LGI1 antibodies 1
- Cerebrospinal fluid (CSF) analysis to detect inflammatory changes like elevated protein levels, pleocytosis, and oligoclonal bands, as well as to test for NAAs panel 1
- Brain MRI to identify inflammation patterns and rule out other causes
- EEG to detect abnormal brain electrical activity characteristic of encephalitis
- Comprehensive imaging studies, including CT scans, PET scans, mammography, ultrasound, and other cancer-specific screenings, to identify the underlying cancer 1
Importance of Early Diagnosis
Early diagnosis is critical as prompt treatment of both the underlying cancer and the immune response can significantly improve outcomes. A multidisciplinary approach involving neurologists, oncologists, and immunologists is typically required for effective management.
Screening for Associated Neoplasm
Cancer screening should be considered in most adult patients with autoimmune encephalitis at the time of presentation, with the most common neoplasms associated with AE including small cell lung cancer, thymic neoplasm, breast cancer, ovarian teratoma or carcinoma, testicular teratoma or seminoma, neuroblastoma, and lymphoma 1. Initial screening with CT of the chest, abdomen, and pelvis with contrast is a reasonable approach, given its lower cost compared with FDG-PET and since it provides more structural details of the neoplasm to guide biopsy and further surgical intervention if indicated.
From the Research
Diagnostic Tests for Paraneoplastic Encephalitis
To diagnose paraneoplastic encephalitis, several tests can be utilized, including:
- Neuropathological examination
- Presence of a compatible clinical picture
- Interval of less than 4 years between the development of neurological symptoms and tumor diagnosis
- Exclusion of other neuro-oncological complications
- Cerebrospinal fluid (CSF) analysis with inflammatory changes but negative cytology
- Magnetic resonance imaging (MRI) demonstrating temporal lobe abnormalities
- Electroencephalogram (EEG) showing epileptic activity in the temporal lobes
- Detection of antineuronal antibodies, such as anti-Hu, anti-Ta, anti-Ma, anti-NMDA receptor, anti-Yo, anti-CV2, anti-Ri, and anti-Tr antibodies 2, 3, 4, 5
Role of Antibodies in Diagnosis
Antibodies play a crucial role in the diagnosis of paraneoplastic encephalitis. The presence of specific antibodies can help establish the diagnosis and predict the underlying tumor type. For example:
- Anti-Hu antibodies are often associated with small-cell lung cancer
- Anti-Ta antibodies are associated with testicular tumors
- Anti-Ma antibodies are associated with various tumor types, including breast, lung, and colon cancer
- Anti-NMDA receptor antibodies are associated with ovarian teratoma and other tumor types 2, 3, 4
Imaging and Laboratory Tests
Imaging tests, such as MRI, can help identify temporal lobe abnormalities and other changes suggestive of paraneoplastic encephalitis. Laboratory tests, including CSF analysis and EEG, can also provide valuable information to support the diagnosis. CSF analysis may show inflammatory changes, such as pleiocytosis and elevated protein levels, while EEG may show epileptic activity in the temporal lobes 2, 5
Standard Operating Procedure for Diagnosis
A standard operating procedure (SOP) for the diagnosis of antibody-associated autoimmune encephalitis, including paraneoplastic encephalitis, has been established. The SOP includes the following steps:
- Recognition of clinical symptoms and initiation of relevant antibody diagnostics
- Confirmation of the clinical diagnosis
- Therapeutic decisions, including immunotherapy and tumor screening
- Exclusion of differential diagnoses 6