Management of Autoimmune Paraneoplastic Encephalitis (Cited Evidence)
Diagnostic Evaluation
Neuroimaging and Electrophysiology
- Brain MRI and EEG should be performed to detect focal or multifocal abnormalities that support the diagnosis of autoimmune encephalitis. 1, 3
Cerebrospinal Fluid Assessment
- Lumbar puncture is required to confirm an inflammatory process, exclude infectious or neoplastic mimics, and to test CSF for oligoclonal bands, IgG index, IgG synthesis rate, and neuronal autoantibodies. 4, 1
Serum Antibody Testing
- Serum neuronal autoantibody panels should be sent in parallel with CSF testing to increase diagnostic yield. 1, 3
Advanced Metabolic Imaging
- Brain ^18F‑FDG PET is recommended when clinical suspicion remains high but MRI/EEG/CSF are nondiagnostic. 1, 5
Cancer Screening Protocol
- All patients with suspected paraneoplastic encephalitis require comprehensive contrast‑enhanced CT of the chest, abdomen, and pelvis. 1, 3
- If the initial CT is negative, additional imaging (mammography or breast MRI, pelvic ultrasound, and/or whole‑body FDG‑PET) should be added based on the specific antibody profile and individual cancer‑risk factors. 1, 5
Acute Immunotherapy
First‑Line Treatment
- High‑dose intravenous methylprednisolone should be started immediately after infection has been excluded by basic CSF analysis. 1, 2, 5
- When steroids are contraindicated, intravenous immunoglobulin (IVIG) or plasma exchange (PLEX) may be used as alternative first‑line agents. 1, 3
Steroid Contraindications
- Relative contraindications to high‑dose steroids include uncontrolled hypertension, uncontrolled diabetes, active peptic ulcer disease, and severe behavioral symptoms that worsen with corticosteroids. 2, 6
Escalation for Non‑Responders
- If there is no clinical improvement after initial first‑line therapy, IVIG or PLEX should be added. 1, 7, 3
- IVIG is preferred first in patients who are agitated or have bleeding disorders. 1, 8
- PLEX (5–10 sessions every other day) is preferred first in patients with severe hyponatremia, high thromboembolic risk (e.g., known or suspected cancer, smoking, hypertension, diabetes, hyperlipidaemia), or concurrent demyelinating disease. 1, 2, 8
- High thromboembolic risk patients are defined as those with known or suspected malignancy, a smoking history, hypertension, diabetes, hyperlipidaemia, or hypercoagulable states. 2, 6
Second‑Line Immunotherapy (2–4 weeks after failed acute therapy)
- For classical paraneoplastic syndromes associated with intracellular antibodies, cyclophosphamide should be initiated given the cell‑mediated autoimmune mechanism. 1, 2
- For antibody‑mediated autoimmunity targeting surface antigens, rituximab is the recommended second‑line agent. 1, 2
Refractory Cases
- In patients who do not respond to rituximab or cyclophosphamide, consider off‑label use of tocilizumab (IL‑6 receptor antagonist) or bortezomib (proteasome inhibitor), acknowledging that supporting evidence is limited. 4, 1
Severe Presentations Requiring Up‑Front Combination Therapy
- In severe NMDAR‑antibody encephalitis, new‑onset refractory status epilepticus (NORSE), or similarly fulminant presentations, initiate combination therapy (steroids + IVIG or steroids + PLEX) from the outset rather than sequentially. 1, 7, 8