Cancer markers in spinal fluid may reveal tumors mistaken for autoimmune encephalitis

A University of Kentucky neurologist proposes a new diagnostic method that could expedite the identification of brain cancers, potentially avoiding months of unnecessary treatment for autoimmune encephalitis. In a study published in the Journal of the Neurological Sciences, Jagannadha Jay Avasarala, M.D., suggests integrating cerebrospinal fluid (CSF) liquid biopsy into the evaluation of patients with suspected autoimmune encephalitis.

Autoimmune encephalitis is a condition where the immune system mistakenly attacks the brain, leading to symptoms like memory loss, seizures, and altered consciousness. Since these symptoms can also be caused by certain brain and central nervous system cancers that may resemble inflammation on brain imaging and spinal fluid tests, misdiagnosis can occur.

When antibody testing for autoimmune encephalitis is negative, known as seronegative autoimmune encephalitis, underlying tumors might be overlooked. The proposed workflow aims to enhance early detection of these tumors, ultimately saving lives. Current diagnostic methods primarily focus on identifying antibodies associated with autoimmune encephalitis, often failing to detect underlying tumors.

Research cited in the paper reveals that brain tumors accounted for 9.5% of such misdiagnoses, with patients waiting a median of 16 months for the correct diagnosis. One in five patients in the study experienced complications from unnecessary immunotherapy. Avasarala's approach utilizes liquid biopsy to identify genetic and molecular markers of cancer within the CSF.

As CSF is often collected during a spinal tap for autoimmune encephalitis evaluation, additional molecular testing could uncover cancers that conventional tests may miss. The tests already exist and are commercially available, with some providing results within hours. Five warning signs suggest doctors should consider liquid biopsy testing: unusual symptoms in patients testing negative for known antibodies, unclear MRI findings, lack of response to initial treatment, current or previous cancer diagnosis, and inflammatory CSF when conventional cancer testing is negative.

Avasarala emphasizes that this isn't about adding a test for every patient, but rather recognizing when a broader search is needed to ensure an underlying cancer isn't being missed.