From the Guidelines
For a patient with symptoms of autoimmune encephalitis but normal brain imaging and negative CSF antibody studies, further evaluation should include serum antibody panels for both neuronal surface and intracellular antigens, as some antibodies may be detected in serum but not CSF, as recommended by the best practice guidelines for diagnosis and acute management of autoimmune encephalitis 1. The diagnostic workup for autoimmune encephalitis should follow a structured approach, starting with brain imaging and cerebrospinal fluid (CSF) analysis, and then considering other investigations such as serum antibody panels, whole body imaging, and EEG monitoring 1. Important considerations in the diagnostic workup include:
- Repeat CSF studies with expanded antibody testing at a specialized neuroimmunology laboratory, as commercial panels may miss rare antibodies
- Whole body imaging (CT chest/abdomen/pelvis or PET) to search for occult malignancies that can trigger paraneoplastic syndromes
- EEG monitoring to reveal characteristic patterns even with normal imaging Autoimmune encephalitis can be seronegative in up to 30% of cases, and early treatment significantly improves outcomes even before definitive diagnosis, making a trial of immunotherapy (IV methylprednisolone 1g daily for 3-5 days) a diagnostic and therapeutic option in suspected autoimmune cases despite negative workup 1. Other conditions that can mimic autoimmune encephalitis include:
- Infectious encephalitis (viral, bacterial, fungal)
- Toxic-metabolic encephalopathy (from medications, substances, or metabolic derangements)
- Psychiatric disorders (particularly first-episode psychosis)
- Prion diseases
- Primary CNS lymphoma
- Status epilepticus
- Certain genetic or metabolic disorders It is essential to consider these mimics in the diagnostic workup and to rule out other potential causes of the patient's symptoms, as recommended by guidelines for the management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy 1.
From the Research
Further Studies
To further investigate the patient's condition, the following studies can be considered:
- Repeat CSF studies to identify any antibodies that may have been missed initially 2
- Perform electroencephalography (EEG) to evaluate for any abnormal brain activity 3
- Conduct a thorough cancer screening, as some forms of autoimmune encephalitis are associated with underlying neoplasia 4, 3
- Consider advanced imaging techniques, such as functional MRI or PET scans, to evaluate for any subtle abnormalities in brain function or structure 2
Autoimmune Encephalitis Mimics
Autoimmune encephalitis can be mimicked by various other conditions, including:
- Infectious encephalitis, which can present with similar symptoms and require prompt treatment 3
- Primary psychiatric illnesses, such as schizophrenia or bipolar disorder, which can have overlapping symptoms with autoimmune encephalitis 2
- Other neurological disorders, such as multiple sclerosis or neurodegenerative diseases, which can have similar clinical presentations 5
- Metabolic or toxic disorders, which can cause encephalopathy and mimic autoimmune encephalitis 6