| Framework/source | Treatment tier / decision point | Recommended strategy | Timing for escalation / treatment failure | Dosing examples provided | Neoplasm / other key management notes | Source URL + publication date |
|---|---|---|---|---|---|---|
| Canadian consensus guidelines | Empiric initiation | Start **early empiric immunotherapy** for suspected autoimmune encephalitis once infectious causes are reasonably excluded; **do not delay while awaiting neural antibody results** (pqac-00000008, pqac-00000009) | Treatment should begin promptly in the acute setting; delay is associated with worse prognosis in guideline rationale (pqac-00000005, pqac-00000009) | Severe AIE combination therapy example: **IV methylprednisolone 1 g daily for 5 days** plus **IVIG 2 g/kg over 2–5 days** (pqac-00000009) | **Early tumor removal in paraneoplastic encephalitis is crucial**; malignancy search is part of workup, especially with intermediate/high-risk neural antibodies (pqac-00000009) | https://doi.org/10.1017/cjn.2024.16; Feb 2024 (pqac-00000008, pqac-00000009) |
| Canadian consensus guidelines | First-line therapy | Steroids, IVIG, and/or plasma exchange (PLEX); in severe disease, guideline supports **combination therapy** rather than waiting for monotherapy failure (pqac-00000008, pqac-00000009) | **First-line failure** defined as lack of improvement or worsening at **5–10 days in severe AIE** and **2–4 weeks in mild/moderate AIE**; objective measures such as seizure frequency and cognitive testing recommended (pqac-00000008) | **IV methylprednisolone 1 g/day ×5 days**; **IVIG 2 g/kg over 2–5 days**; repeat high-dose steroids or repeat PLEX/IVIG can be considered if previously effective (pqac-00000008, pqac-00000009) | Follow-up MRI if initial MRI negative but suspicion remains; FDG-PET may be more sensitive than MRI but should not be used alone for diagnosis (pqac-00000009) | https://doi.org/10.1017/cjn.2024.16; Feb 2024 (pqac-00000008, pqac-00000009) |
| Canadian consensus guidelines | Second-line therapy: cell-surface antibody or antibody-negative AIE | Prefer **rituximab** because of efficacy/safety profile in cell-surface antibody disease and antibody-negative AIE (pqac-00000008) | Escalate after first-line failure using above timing windows; failure after second-line is harder to define because onset of action is variable and treatments overlap (pqac-00000008) | Specific rituximab dose not stated in extracted Canadian text (pqac-00000008) | Can use rituximab when cyclophosphamide is contraindicated (pqac-00000008) | https://doi.org/10.1017/cjn.2024.16; Feb 2024 (pqac-00000008) |
| Canadian consensus guidelines | Second-line therapy: paraneoplastic / intracellular high-risk antibody AIE | Prefer **cyclophosphamide** for paraneoplastic cases and intracellular high-risk antibodies such as **Hu** or **Yo** (pqac-00000008) | Escalate after first-line failure; specialist input recommended in severe/refractory disease (pqac-00000008) | Specific cyclophosphamide dose not stated in extracted Canadian text (pqac-00000008) | Strong recommendation for **tumor resection and oncology involvement** in paraneoplastic encephalitis (pqac-00000008, pqac-00000009) | https://doi.org/10.1017/cjn.2024.16; Feb 2024 (pqac-00000008, pqac-00000009) |
| Canadian consensus guidelines | Third-line / refractory disease | **Tocilizumab** or **bortezomib** used for refractory disease after failure of second-line therapy; myeloablative cyclophosphamide may be considered in selected severe cases with specialist input (pqac-00000008) | No fixed universal failure interval after second-line because response kinetics vary (pqac-00000008) | Specific tocilizumab/bortezomib doses not stated in extracted Canadian text (pqac-00000008) | Guideline notes evidence base is limited and largely observational/consensus-driven, except one positive RCT for IVIG in LGI1/CASPR2-seropositive patients (pqac-00000009) | https://doi.org/10.1017/cjn.2024.16; Feb 2024 (pqac-00000008, pqac-00000009) |
| Brazilian consensus recommendations | Empiric initiation | Treat **possible or definite AIE**; consensus states **treatment should be started within the first 4 weeks of symptoms** and should not wait for complete antibody confirmation when suspicion is high (pqac-00000010, pqac-00000012, pqac-00000013) | If there is **no satisfactory clinical/functional improvement within 10–14 days**, start second-line therapy (pqac-00000012) | First-line usually combines methylprednisolone with IVIG or plasmapheresis (pqac-00000010, pqac-00000011) | Prognosis is associated with treatment within the first 4 weeks; panel recommends neoplasm screening at presentation (pqac-00000013) | https://doi.org/10.1055/s-0044-1788586; Jul 2024 (pqac-00000010, pqac-00000011, pqac-00000012, pqac-00000013) |
| Brazilian consensus recommendations | First-line therapy | Preferred first-line is **combination therapy**: **methylprednisolone + IVIG** or **methylprednisolone + plasmapheresis**; MP, IVIG, and PLEX may be given concomitantly depending on availability/experience (pqac-00000010, pqac-00000011, pqac-00000012, pqac-00000013) | Assess for clinical/functional response over **10–14 days** (pqac-00000012) | **IVIG 2 g/kg over 2–5 days**; **IV methylprednisolone adults 1,000 mg/day for 3–5 days**; **children 20–30 mg/kg/day, max 1 g/day for 3–5 days**; **plasmapheresis 5–7 sessions over 7–14 days** (pqac-00000011) | Rule out herpesvirus encephalitis with CSF PCR; MRI/EEG/CSF are part of parallel workup (pqac-00000011, pqac-00000012) | https://doi.org/10.1055/s-0044-1788586; Jul 2024 (pqac-00000011, pqac-00000012) |
| Brazilian consensus recommendations | Second-line therapy | **Rituximab and/or cyclophosphamide** for refractory disease or inadequate response to first-line therapy (pqac-00000010, pqac-00000011, pqac-00000013) | Start after **10–14 days** without satisfactory improvement (pqac-00000012) | **Rituximab**: acceptable regimens include **500–1,000 mg twice 2 weeks apart** or **375 mg/m² weekly ×4**; **cyclophosphamide 500–1,000 mg/m² IV monthly pulses** (pqac-00000011) | Rituximab supported by better functional outcomes and fewer relapses, especially in anti-NMDAR; cyclophosphamide favored when rituximab unavailable or in selected refractory patients >16 years (pqac-00000011, pqac-00000013) | https://doi.org/10.1055/s-0044-1788586; Jul 2024 (pqac-00000011, pqac-00000013) |
| Brazilian consensus recommendations | Third-line therapy | **Tocilizumab** and **bortezomib** are third-line options for refractory disease (pqac-00000010, pqac-00000011, pqac-00000013) | Used after failure of second-line therapy in refractory cases (pqac-00000010, pqac-00000011) | **Tocilizumab**: monthly IV dosing with pediatric/adult weight-based regimens; **bortezomib**: **3 cycles of 21 days**, given **subcutaneously on days 1, 4, 8, 11** (pqac-00000011) | Intended for highly refractory disease; evidence base remains limited compared with first-/second-line treatments (pqac-00000011, pqac-00000013) | https://doi.org/10.1055/s-0044-1788586; Jul 2024 (pqac-00000011, pqac-00000013) |
| Brazilian consensus recommendations | Maintenance / long-term therapy | Maintenance may include **monthly IVIG** in selected cases; routine long-term **azathioprine/mycophenolate** is **not supported by current evidence**, and oral immunosuppressants should not be used in anti-NMDAR according to panel consensus (pqac-00000010, pqac-00000012, pqac-00000013) | Long-term strategy individualized after acute response (pqac-00000012) | No standardized dose extracted for monthly IVIG maintenance (pqac-00000012) | ASMs are for seizure control; most seizures are acute symptomatic and may be weaned after acute stage (pqac-00000010, pqac-00000011, pqac-00000013) | https://doi.org/10.1055/s-0044-1788586; Jul 2024 (pqac-00000010, pqac-00000011, pqac-00000012, pqac-00000013) |
| Brazilian consensus recommendations | Neoplasm management | Screen for neoplasia at presentation in all patients; for antibodies commonly linked to cancer, continue surveillance (pqac-00000012, pqac-00000013) | Repeat screening **annually for 4 years** when antibodies are commonly tumor-associated (pqac-00000012, pqac-00000013) | Initial screening examples: **contrast-enhanced CT chest/abdomen/pelvis**; MRI if CT contraindicated; consider **whole-body FDG-PET** if CT is negative (pqac-00000013) | Integrates AE care with oncology; parallels Canadian emphasis on early tumor treatment in paraneoplastic disease (pqac-00000008, pqac-00000009, pqac-00000013) | https://doi.org/10.1055/s-0044-1788586; Jul 2024; https://doi.org/10.1017/cjn.2024.16; Feb 2024 (pqac-00000008, pqac-00000009, pqac-00000013) |


*Table: This table summarizes consensus treatment pathways for autoimmune encephalitis and limbic encephalitis from the 2024 Canadian and Brazilian guidelines. It highlights empiric treatment timing, escalation thresholds, drug tiers, dosing examples where available, and tumor-management recommendations.*