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Frequently Asked Questions (FAQs) Is antibody negative (seronegative) AE treated differently than AE with an identified antibody?

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Frequently Asked Questions 


Is antibody negative (seronegative) AE treated differently than AE with an identified antibody?



First let’s clarify what Antibody Negative Autoimmune Encephalitis is to avoid confusion.

As described in A Clinical Approach to Diagnosis of Autoimmune Encephalitis published in 2016.


Criteria for autoantibody-negative but probable autoimmune encephalitis

Diagnosis can be made when all four of the following criteria have been met:

  1. Rapid progression (less than 3 months) of working memory deficits (short-term memory loss), altered mental status, or psychiatric symptoms
  2. Exclusion of well-defined syndromes of autoimmune encephalitis (eg, typical limbic encephalitis, Bickerstaff’s brainstem encephalitis, acute disseminated encephalomyelitis)
  3. Absence of well characterized autoantibodies in serum and CSF, and at least two of the following criteria:
    • MRI abnormalities suggestive of autoimmune encephalitis*
    • CSF pleocytosis, CSF-specific oligoclonal bands or elevated CSF IgG index, or both*
    • Brain biopsy showing inflammatory infiltrates and excluding other disorders (eg, tumor)
  4. Reasonable exclusion of alternative causes


Once diagnosis with standard tests (example, MRI, CSF, or EEG studies) and clinical presentation outlined above have been determined, doctors begin immunotherapy treatment. There is no difference in the treatment protocol for a patient with an identified antibody verses a patient with an unidentified antibody.

Clinical facts and evidence suggest that early immunotherapy improves outcome. Therefore, experts in autoimmune neurology emphasize that the treating doctor not wait for antibody testing results to come back, as this can take 10 days. Using this approach, allows the initiation of preliminary treatment while other studies and comprehensive antibody tests are processed and subsequently used to refine the diagnosis and treatment.  In addition, because not all antibodies in AE have been identified, the patient does not need a positive antibody test to confirm the diagnosis.

The goal of immunotherapy is to provide maximum response, reducing nervous system inflammation and decreasing symptoms, maintain improvements by preventing relapses, and minimize side effects. Following antibody titers in the management of patients has several limitations and rarely helps guide therapy, which should be based on clinical findings as titers are not reliable markers of disease severity, but they can sometimes predict relapses and support the use of prolonged immunotherapy for prevention.

The kind of immunotherapy used for a patient is based on the test results and the patient’s clinical condition. Patients with antibodies with a cancerous tumor, onconeural antibodies, can have limited response to immunotherapy but can stabilize with tumor removal. Immunotherapy can be tried with often limited success. In addition to immunotherapy, other important aspects of the treatment include supportive care, particularly in the inpatient setting, symptomatic therapy (seizures, spasms, neuropsychiatric symptoms) and rehabilitation.



A clinical approach to diagnosis of autoimmune encephalitis

Diagnostic and Therapeutic Approach to Autoimmune Neurologic Disorders A. Sebastian López-Chiriboga, MD Eoin P. Flanagan, MD

Clinical, radiological and laboratory comparison between autoantibody-negative and autoantibody-positive Autoimmune Encephalitis patients. (P2.2-006)


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