Autoimmune Encephalitis Diagnosis and Treatment
Introduction to Autoimmune Encephalitis
- The presence of high levels of IgE against streptococcus and IgG antibodies against brain components (anti-tubulin, anti-myelin, anti-dopamine receptors) strongly suggests post-infectious autoimmune encephalitis, requiring urgent neurological evaluation and immunosuppressive treatment, as recommended by the American Academy of Neurology 1, 2
Diagnostic Evaluation
- Brain MRI with contrast is recommended to evaluate possible alterations in the hippocampus, striatum, or other brain areas, with a strength of evidence level of B, according to the American Academy of Neurology 3
- Lumbar puncture for CSF analysis, including cell count and differential, protein, glucose, and IgG index, is essential for diagnosing autoimmune encephalitis, with a strength of evidence level of A, according to the American Academy of Neurology 4
- PCR for viral infections (HSV1/2, VZV) should be performed to exclude infectious causes, with a strength of evidence level of A, according to the Infectious Diseases Society of America 4
- A panel of neuronal antibodies in CSF and serum should be tested, including anti-NMDAR, anti-VGKC, anti-LGI1, and anti-CASPR2, with a strength of evidence level of B, according to the American Academy of Neurology 3, 5
Treatment
- High-dose corticosteroids (0.5 mg/kg/day of prednisone or methylprednisolone) are recommended as first-line treatment, with a strength of evidence level of A, according to the American Academy of Neurology 1, 6
- Intravenous immunoglobulins (IVIg) (0.4 g/kg/day for 5 days) may be used in acute or severe cases, with a strength of evidence level of B, according to the American Academy of Neurology 1, 6
- Plasma exchange may be considered as an alternative or in addition to IVIg in non-responders, with a strength of evidence level of C, according to the American Academy of Neurology 6
Monitoring and Prognosis
- Regular monitoring of antibody levels in serum is essential to evaluate treatment efficacy, with a strength of evidence level of B, according to the American Academy of Neurology 7
- Periodic neurological evaluation is necessary to monitor symptom improvement, with a strength of evidence level of A, according to the American Academy of Neurology 1
- Repeat brain MRI after 3-6 months of treatment is recommended, with a strength of evidence level of B, according to the American Academy of Neurology 3
- Early immunosuppressive treatment is associated with significant improvement in outcomes, with a strength of evidence level of A, according to the American Academy of Neurology 1
- Confusion and seizures often improve rapidly with immunosuppression, while memory recovery may take months or years, with a strength of evidence level of B, according to the American Academy of Neurology 1
Diagnostic Approach to Autoimmune Encephalitis
Initial Evaluation
- The American Academy of Neurology recommends ordering serum neuronal autoantibodies panel along with targeted blood tests to exclude competing etiologies, with samples collected before any immunotherapy administration 8, 9
- Collecting blood samples before administering intravenous immunoglobulins or plasmapheresis is crucial to avoid false positive or false negative results 8, 9
Essential Exclusionary Tests
- Antinuclear antibodies (ANA) should be ordered as part of the exclusionary tests to rule out other autoimmune conditions 8
- Extractable nuclear antigen (ENA) antibodies should be ordered to exclude other autoimmune conditions 8
- Antiphospholipid antibodies should be ordered to exclude other autoimmune conditions 8
- Lupus anticoagulant should be ordered to exclude other autoimmune conditions 8
- Vitamin B1 (thiamine) level should be checked as part of the metabolic/nutritional workup 9
- Ammonia level should be checked as part of the metabolic/nutritional workup 8
- Metabolic panel (comprehensive) should be ordered to rule out other metabolic conditions 9
- Hormonal panels should be ordered when clinically indicated 8
- Toxicology screen should be ordered to rule out other causes of encephalitis 9
- Sodium level should be monitored, as hyponatremia is common with LGI-1 antibody encephalitis 8, 9
- Treponemal antibodies (syphilis) should be ordered as part of the infectious workup 9
Testing Nuances
- Testing both serum and CSF is recommended because sensitivity varies by antibody type 8, 10
- Tailoring additional blood tests based on MRI anatomical patterns is recommended, though comprehensive testing is warranted even with negative MRI 8, 9
- The American Academy of Neurology recommends against delaying antibody testing if CSF shows normal cell counts, as autoimmune encephalitis can present with normal routine CSF studies 8, 9
- The American Academy of Neurology recommends against relying solely on commercial assays, as false negatives occur frequently, especially in CSF samples 8, 10
- The American Academy of Neurology recommends against skipping serum testing, even when CSF is available, as some antibodies are better detected in serum 8, 10
Diagnostic Approach to Autoimmune Encephalitis
Diagnostic Steps
- The diagnosis of autoimmune encephalitis requires a systematic three-step approach: (1) confirm focal or multifocal brain pathology, (2) establish inflammatory etiology while excluding competing diagnoses, and (3) screen for associated malignancy, as recommended by the Journal of Neurology, Neurosurgery and Psychiatry 11
- Brain MRI with or without contrast is the initial imaging modality of choice to evaluate for characteristic patterns including hippocampal, striatal, or other regional abnormalities, according to the Journal of Neurology, Neurosurgery and Psychiatry 11
- EEG should be performed if MRI is negative, if the patient is encephalopathic, or if frequent seizures are occurring, as stated by the Journal of Neurology, Neurosurgery and Psychiatry 11
- Brain FDG-PET is reserved for cases where MRI is negative but clinical suspicion remains high, or when MRI is contraindicated, as noted by the Journal of Neurology, Neurosurgery and Psychiatry 11, 12
Diagnostic Tests
- Focal slowing or seizures, lateralized periodic discharges, and extreme delta brush (particularly in NMDAR-antibody encephalitis) suggest autoimmune encephalitis, according to the Journal of Neurology, Neurosurgery and Psychiatry 11
- A normal EEG does not exclude autoimmune encephalitis, especially in LGI1-antibody encephalitis where patients may have classical faciobrachial dystonic seizures despite normal EEG, as reported by the Journal of Neurology, Neurosurgery and Psychiatry 11, 12
- Lumbar puncture is essential and should include comprehensive CSF analysis: cell count with differential, protein, glucose, IgG index, oligoclonal bands, and neuronal autoantibodies, as recommended by the Journal of Neurology, Neurosurgery and Psychiatry 11
Cancer Screening
- Cancer screening should begin with CT chest, abdomen, and pelvis with contrast, as suggested by the Journal of Neurology, Neurosurgery and Psychiatry 11, 12
- Whole body FDG-PET if initial screening remains negative, as noted by the Journal of Neurology, Neurosurgery and Psychiatry 11
- A targeted screening approach may be implemented when clinical presentation strongly suggests a specific neoplasm (e.g., starting with pelvic ultrasound if anti-NMDAR encephalitis is suspected), according to the Journal of Neurology, Neurosurgery and Psychiatry 11, 12