Autoimmune Encephalitis Panel

Immunity

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Blood test panel for neuronal antibodies.

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Autoimmune Encephalitis Panel - Comprehensive Medical Test Information

Section 1: Why is it done?
- Test Description: The Autoimmune Encephalitis Panel is a specialized blood or cerebrospinal fluid (CSF) test that detects specific autoantibodies associated with autoimmune inflammation of the brain. It identifies antibodies against neuronal surface antigens, intracellular proteins, and other brain-specific targets that trigger immune-mediated encephalitis.
- Primary Indications for Testing:
  - Suspected autoimmune encephalitis presenting with subacute cognitive decline, behavioral changes, or personality alterations
  - Unexplained seizures, particularly refractory or new-onset seizures in adults or children
  - Psychiatric symptoms with concurrent neurological manifestations (psychosis, hallucinations, catatonia)
  - Movement disorders including dystonia, dyskinesias, or abnormal involuntary movements
  - Autonomic dysfunction or sleep disturbances with neurological symptoms
  - Negative infectious workup in patients with encephalitis symptoms
  - Associated malignancies with neurological paraneoplastic syndrome
- Typical Timing and Circumstances: Testing is typically performed acutely during hospitalization when encephalitis is suspected. For CSF testing, lumbar puncture is performed within days of symptom onset. Blood samples can be collected concurrently or as follow-up testing. Testing may be repeated during the disease course to monitor for seroconversion or in patients with initially seronegative but clinically compelling presentations.
Section 2: Normal Range
- Normal/Reference Values:
  - Negative/Undetectable: <0.05 to <0.1 optical density (OD) units or titers <1:10, depending on methodology and specific antibody
  - Units of Measurement: Titers (1:10, 1:32, 1:100, 1:320, etc.), optical density (OD) ratios, or semiquantitative results
- Result Interpretation:
  - Negative Result: No detectable antibodies against the tested antigens. Does not exclude autoimmune encephalitis; may indicate seronegative disease or untested antibody targets.
  - Low-Positive Result (Titer 1:10-1:32): May represent borderline positivity or early seroconversion; CSF positivity is more significant than serum alone; clinical correlation essential.
  - Moderate-to-High Positive Result (Titer ≥1:100): Highly significant; strongly supports diagnosis of autoimmune encephalitis when clinical features are consistent.
- What Normal vs Abnormal Means: Normal (negative) results suggest absence of the detected antibody, but do not exclude autoimmune encephalitis. Abnormal (positive) results indicate presence of autoimmune markers specific to autoimmune encephalitis and suggest immune-mediated brain inflammation. CSF positivity combined with elevated CSF white blood cells, protein, and clinical symptoms is most diagnostic.
Section 3: Interpretation
- Detailed Result Interpretation by Antibody Type:
  - NMDA Receptor Antibodies: Positive results indicate anti-NMDA receptor encephalitis, characterized by psychiatric symptoms, seizures, movement disorders, autonomic instability, and decreased consciousness. Often affects young females. Strong association with ovarian teratomas (30-40% of cases). CSF positivity is more specific than serum.
  - LGI1 and Caspr2 Antibodies: Positive results indicate autoimmune limbic encephalitis or Morvan syndrome. Associated with seizures, memory impairment, autonomic dysfunction, and sleep disturbances. Often found in older adults; rarely associated with malignancy. LGI1 alone suggests faciobrachial dystonic seizures.
  - GABA-B Receptor Antibodies: Positive results indicate GABA-B receptor-associated encephalitis with prominent seizures, limbic encephalitis, and brainstem signs. Frequently associated with small cell lung cancer (50-80% of cases). Requires urgent malignancy screening.
  - AMPA Receptor Antibodies: Positive results indicate AMPA receptor encephalitis with progressive cognitive decline, seizures, and psychiatric manifestations. Associated with malignancy in 60-80% of cases, particularly lung and breast cancers.
  - GABAergic Synapse Antibodies (Gephyrin, Collybistin): Positive results indicate progressive encephalomyelitis with rigidity or autoimmune stiff person syndrome spectrum. Associated with seizures, stiffness, and autonomic dysfunction; malignancy found in 10-40% of cases.
  - DPPX Antibodies: Positive results indicate DPPX encephalitis with severe diarrhea, tremor, ataxia, seizures, and encephalopathy. Rarely associated with malignancy; autoimmune mediated disease.
- Factors Affecting Result Interpretation:
  - Specimen type (CSF vs serum): CSF positivity is more clinically significant and specific than serum positivity alone
  - Timing of sampling: Early samples (first week) may be negative due to seroconversion delay; repeat testing may be needed at 2-4 weeks
  - Immunosuppressive therapy: May reduce antibody levels; should not delay testing, but may cause false negatives if already initiated
  - Laboratory methodology: Different assays (immunofluorescence, cell-based assays, ELISA) have varying sensitivities and specificities
  - Clinical presentation: Results must be interpreted alongside CSF pleocytosis, MRI abnormalities, and characteristic clinical features
- Clinical Significance of Result Patterns:
  - Single positive antibody: Diagnostic when clinical and CSF features are consistent; initiates specific treatment and malignancy screening based on antibody type
  - Multiple positive antibodies: Uncommon but possible; suggests broader autoimmune process or testing overlap; requires careful interpretation
  - Seronegative disease: Negative panel with clinical encephalitis suggests untested antibodies (e.g., additional NMDA epitopes) or truly seronegative autoimmune encephalitis; empirical immunotherapy still indicated if clinical suspicion high
Section 4: Associated Organs
- Primary Organ System Involved: Central nervous system (brain, particularly limbic structures including hippocampus and amygdala, though can affect entire brain and brainstem). Secondary involvement of peripheral nervous system (autonomic dysfunction) and muscle in specific syndromes.
- Medical Conditions Associated with Abnormal Results:
  - Paraneoplastic Autoimmune Encephalitis: Associated with small cell lung cancer (GABA-B, glutamic acid decarboxylase), breast cancer (AMPA receptor), ovarian teratoma (NMDA receptor), and testicular cancer (GABA-B). Antibody presence mandates comprehensive malignancy screening.
  - Non-Paraneoplastic Autoimmune Encephalitis: LGI1 and Caspr2 antibodies frequently non-paraneoplastic and associated with LEMS or thymoma. NMDA receptor encephalitis without teratoma. DPPX encephalitis typically non-paraneoplastic.
  - Autoimmune Stiff Person Syndrome (GABAergic Synapse Antibodies): Progressive muscle stiffness, rigidity, painful spasms, and hyperreflexia. Can progress to encephalomyelitis with autonomic dysfunction. Associated with diabetes mellitus.
  - Morvan Syndrome (LGI1 or Caspr2): Severe insomnia, hallucinations, confusion, seizures, autonomic hyperactivity with sweating and tachycardia, and neuromyotonia.
- Diseases Helped by This Test Diagnosis:
  - Anti-NMDA receptor encephalitis
  - Anti-LGI1/Caspr2 encephalitis and Morvan syndrome
  - Anti-GABA-B receptor encephalitis
  - Anti-AMPA receptor encephalitis
  - Anti-DPPX encephalitis
  - Autoimmune stiff person syndrome and its spectrum (progressive encephalomyelitis with rigidity)
  - Paraneoplastic autoimmune encephalitis (various cancer types)
- Potential Complications Associated with Abnormal Results:
  - Severe cognitive impairment and permanent memory loss
  - Drug-resistant seizures with status epilepticus risk
  - Autonomic dysfunction including hypertension, arrhythmias, and sudden cardiac death in severe cases
  - Hypoventilation requiring mechanical ventilation (particularly anti-NMDA receptor)
  - Catatonia, psychiatric hospitalization, and behavioral emergency
  - Movement disorders including severe dyskinesia or dystonia
  - Underlying malignancy complications and treatment-related morbidity
Section 5: Follow-up Tests
- Additional Tests Based on Positive Results:
  - Expanded Autoimmune Serology: Testing for additional neuronal antibodies (e.g., anti-CRMP5, anti-Hu, anti-Yo, anti-CV2) if initial panel negative but clinical suspicion remains high.
  - Malignancy Screening (Based on Antibody Type):
    - GABA-B antibodies: High-resolution chest CT for small cell lung cancer; consider abdominal/pelvic imaging
    - NMDA antibodies: Pelvic ultrasound or MRI for ovarian teratoma; consider chest imaging
    - AMPA antibodies: Chest CT and breast imaging; consider malignancy screening panel
    - LGI1/Caspr2: Less frequently paraneoplastic; standard age-appropriate cancer screening
  - CSF Analysis: Cell count and differential, protein, glucose, oligoclonal bands, and intrathecal immunoglobulin synthesis. CSF antibody testing often more sensitive than serum.
  - Brain MRI: To identify limbic encephalitis (hippocampal or amygdala changes), brainstem involvement, or structural lesions. T2/FLAIR abnormalities help confirm encephalitis.
  - EEG: To detect seizure activity, characterize abnormal rhythms (delta activity, slowing), and differentiate seizures from non-epileptic events. May show extreme delta brush pattern in anti-NMDA receptor disease.
  - EMG/NCS: If suspicion for neuromyotonia or peripheral nerve involvement (LGI1, Caspr2, GABAergic synapse antibodies).
- Monitoring Frequency for Ongoing Conditions:
  - Acute Phase (First Month): Clinical assessment weekly to biweekly. Repeat CSF analysis if deterioration or concerning features (hemorrhage, rising protein). Repeat serum/CSF antibodies at 2-4 weeks if initially negative.
  - Maintenance Phase (First 6 Months): Monthly or quarterly clinical evaluation. Brain MRI every 3-6 months if actively treating. EEG as needed for seizure management.
  - Long-term Follow-up (6+ Months): Every 6-12 months or as clinically indicated. Continued tumor surveillance if malignancy-associated. Neuropsychological testing to assess for cognitive recovery.
- Related Complementary Tests:
  - Infectious disease workup: Blood and CSF cultures, viral PCR panel (HSV, VZV, enterovirus, COVID-19), bacterial PCR, fungal and tuberculous testing to exclude infectious mimics
  - General autoimmune serology: ANA, anti-thyroid antibodies, complement levels if systemic autoimmune disease suspected
  - PET scan: Fluoro-deoxyglucose PET for detection of occult malignancy or assessment of disease activity
  - Testicular/Ovarian ultrasound: Specific imaging for antibody-associated teratomas or testicular malignancies
Section 6: Fasting Required?
- Fasting Requirement: No
- Explanation: Fasting is not required for the Autoimmune Encephalitis Panel. This antibody testing is not affected by food or beverage intake. Patients can eat and drink normally before blood collection.
- Medications to Avoid:
  - Patients should not discontinue prescribed medications before testing. Continue all routine medications including anticonvulsants, immunosuppressants, antibiotics, and other therapies without modification.
  - Note: Immunosuppressive therapy (corticosteroids, IVIG, plasmapheresis) may reduce antibody titers but should not delay or prevent testing. Inform the laboratory of recent immunosuppressive treatment.
- Special Patient Preparation Requirements:
  - For Blood Samples: Standard venipuncture; no special preparation needed. Patient should be informed testing is being performed for antibody detection.
  - For CSF Samples: Lumbar puncture required; performed by physician or trained clinician. Patient should empty bladder before procedure. Informed consent required. Patient should lie flat for 30 minutes post-procedure to minimize post-LP headache. Adequate hydration recommended. Some patients may experience mild discomfort or transient leg pain.
  - Sample Handling: Samples should be kept at room temperature or refrigerated depending on laboratory protocol. Do not freeze samples unless instructed. Transport to laboratory as quickly as possible (ideally within 24 hours for CSF, within 48 hours for serum). Clearly label samples with patient identifiers and collection time.
  - Timing of Specimen Collection: Collect samples early in disease course (ideally within first 2-4 weeks of symptom onset). Serum and CSF samples obtained simultaneously or CSF first if available. Early morning collection preferred for consistency.
  - Important Patient Communication: Inform patient that results may take 1-3 weeks or longer as some tests require specialized laboratory techniques. Negative results do not completely exclude autoimmune encephalitis. Discuss that positive results require correlation with clinical presentation, CSF findings, and imaging. If obtaining CSF, explain procedure risks including infection risk (rare), bleeding, post-LP headache, and transient lower extremity symptoms.

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