A University of Kentucky neurologist is proposing a new diagnostic roadmap that could help doctors identify hidden brain cancers earlier and prevent patients from undergoing months of treatment for the wrong condition.
In a paper published in the Journal of the Neurological Sciences, Jagannadha “Jay” Avasarala, M.D., in the UK College of Medicine Department of Neurology, describes a workflow that adds cerebrospinal fluid (CSF) liquid biopsy to the evaluation of certain patients with suspected autoimmune encephalitis.
Autoimmune encephalitis occurs when the immune system mistakenly attacks the brain, causing symptoms that can include memory and behavioral changes, seizures and altered consciousness. Diagnosing the condition can be difficult because some cancers affecting the brain and central nervous system can cause similar symptoms and even look like inflammation on brain imaging and spinal fluid testing.
Avasarala says current diagnostic approaches are primarily designed to identify antibodies associated with autoimmune encephalitis, rather than cancer. When antibody testing is negative — known as seronegative autoimmune encephalitis — an underlying tumor can sometimes go undetected.
Research cited in the paper illustrates the potential consequences. In the largest multicenter study of autoimmune encephalitis misdiagnosis, brain tumors accounted for 9.5% of misdiagnoses, and patients waited a median of 16 months before receiving the correct diagnosis. One in five patients in the study experienced complications from immunotherapy they did not need.
“This workflow is designed to save lives,” Avasarala said. “We need to recognize when the underlying problem may be cancer and use the tools available to find what might otherwise be missed.”
Avasarala's proposed approach uses liquid biopsy to look for genetic and molecular signs of cancer in CSF, the fluid surrounding the brain and spinal cord. Because CSF is often already collected through a spinal tap when patients are evaluated for autoimmune encephalitis, additional molecular testing could provide another way to search for cancers that conventional testing may miss.
The tests themselves are not experimental. The paper points to validated, commercially available testing methods already incorporated into National Comprehensive Cancer Network guidelines for several cancers affecting the central nervous system. Some targeted tests can return results within hours.
Avasarala identifies five warning signs that should prompt doctors to consider liquid biopsy testing. They include unusual symptoms in patients who test negative for known antibodies, unclear MRI findings, failure to respond to initial treatment, a current or previous cancer diagnosis, and inflammatory spinal fluid when conventional testing for cancer is negative.
“This isn't about adding another test for every patient,” Avasarala said. “It’s about recognizing when we need to broaden the search and make sure an underlying cancer isn't being missed.”