What is the appropriate treatment approach for a patient with suspected paraneoplastic encephalitis?

Treatment of Paraneoplastic Encephalitis

For suspected paraneoplastic encephalitis, immediately initiate immunotherapy with high-dose intravenous corticosteroids while simultaneously pursuing aggressive cancer screening and tumor removal, as neurological outcomes depend critically on early intervention before irreversible neuronal damage occurs.

Immediate Critical Care Management

Patients with declining consciousness require urgent ICU assessment for:

• Airway protection and ventilatory support 1
• Management of raised intracranial pressure and optimization of cerebral perfusion pressure 1
• Correction of electrolyte imbalances 1
• Transfer to a neurological unit within 24 hours if diagnosis is unclear or patient fails to improve 1

Diagnostic Workup for Paraneoplastic Etiology

When paraneoplastic encephalitis is suspected, specific investigations include:

• Anti-neuronal and onconeuronal antibodies (Hu, Yo, Ri, NMDA receptor, voltage-gated potassium channel complex, N-type voltage-gated calcium channel) in serum and CSF 1
• CT or PET scan of chest, abdomen, and pelvis to identify occult malignancy 1
• Alpha fetoprotein and beta-human chorionic gonadotropin for germ cell tumors 1
• MRI brain should be obtained within 48 hours as the primary imaging modality 2
• CSF examination with results available within 24-48 hours 1
• Biopsy of non-CNS viscera when tumor is identified 1

The most commonly associated malignancies are small-cell lung cancer and testicular cancer, though ovarian and other cancers can also be causative 3, 4.

Immunotherapy Protocol

High-dose intravenous methylprednisolone should be initiated immediately as first-line therapy 2. The evidence strongly supports early immunomodulation:

• Intravenous immunoglobulin (IVIG) has demonstrated efficacy, particularly in cases with surface antigen antibodies 3, 5
• Plasmapheresis can produce dramatic clinical improvement within 2 weeks when combined with tumor treatment 4
• Corticosteroids (such as prednisolone 60-80mg daily for 3-5 days) are recommended for inflammatory encephalitic lesions 1

The type of antibody determines treatment responsiveness: antibodies against ion channels and surface antigens (e.g., NMDA receptor) respond well to immunotherapy, while classical onconeuronal antibodies (Hu, Yo, Ri) have poor treatment outcomes 5.

Tumor Management

Definitive treatment requires identification and ablation of the underlying tumor 6:

• Surgical debulking should be performed urgently when tumor is identified 4
• Chemotherapy for the primary malignancy should be initiated promptly 3
• Early tumor treatment combined with immunotherapy translates into more favorable neurological outcomes 3

One case demonstrated complete resolution of seizures and improved mental status within 2 weeks of tumor surgery combined with plasmapheresis and chemotherapy 4.

Seizure Management

If seizures are present:

• IV levetiracetam 30-60 mg/kg/day (73% seizure cessation rate) 2
• IV valproate 20-30 mg/kg loading dose (88% seizure cessation within 20 minutes) 2
• Avoid phenytoin as first-line (only 56% efficacy with 12% hypotension risk) 2
• Anti-epileptic drugs alone are often refractory without addressing the underlying paraneoplastic process 3

Multidisciplinary Care Requirements

Management requires coordinated input from 1, 2:

• Neurologists
• Infectious disease physicians (to exclude infectious mimics)
• Oncologists
• Neuroradiologists
• Intensive care specialists
• Neurophysiologists for EEG monitoring

Critical Pitfalls to Avoid

• Do not delay immunotherapy while awaiting antibody results - treatment should begin on clinical suspicion 3
• Do not assume psychiatric presentation excludes organic disease - paraneoplastic limbic encephalitis commonly mimics primary psychiatric illness 6
• Do not discharge without comprehensive cancer screening - the encephalitis may herald a life-threatening but treatable malignancy 6
• Do not rely on CT brain alone - MRI detects early changes in 90% versus only 25% for CT 2

Rehabilitation and Follow-up

• All patients require comprehensive rehabilitation assessment as 30-50% develop long-term neurological or psychiatric sequelae 2
• Monitor for anxiety, depression, obsessive behaviors, and cognitive deficits which often emerge after discharge 2
• Outpatient follow-up plans should be formulated at discharge with at least one scheduled appointment 1, 7

Prognosis Considerations

Prognosis depends critically on timing of intervention 3. Patients with antibodies against surface antigens have better outcomes with immunotherapy compared to those with classical onconeuronal antibodies 5. However, even with effective treatment, some patients retain residual deficits and recurrences have been described 5.