SRSE/NORSE Treatment
4 / 4 Steps
Super-Refractory Status Epilepticus Treatment Options
Experimental therapies and considerations for super-refractory SE
⚠️ 🔍 🔍 Under Review
This page is currently under review, and most of the treatment options below are experimental and should be considered only after standard treatments have failed, under careful multidisciplinary team judgment.
⚠️ All treatments listed below are EXPERIMENTAL
📚 Please consult with specialists and review the latest literature and guidelines
Super-Refractory Status Epilepticus & NORSE/FIRES Definition
SRSE: Status epilepticus that continues for 24 hours or more despite appropriate anesthetic treatment, or recurs when anesthetics are reduced
NORSE: New-onset refractory status epilepticus without prior epilepsy history
FIRES: Pediatric refractory status epilepticus occurring within 2 weeks of febrile illness
Treatment Options Comparison Table
🧪 EXPERIMENTAL| Treatment Option | Mechanism | Evidence Level | Implementation Difficulty | Key Considerations |
|---|---|---|---|---|
| Methylprednisolone | 1st line immunotherapy - Anti-inflammatory | Level U | Moderate | Recommend starting within 24-72 hours of SE onset (+5) |
| IVIG (Immunoglobulin) | 1st line immunotherapy - Autoantibody neutralization | Level U | Moderate | Effective in autoantibody-mediated encephalitis (+5) |
| Plasmapheresis | 1st line immunotherapy - Rapid autoantibody removal | Level U | High | Faster effect than IVIG in severe cases (+5) |
| Rituximab | 2nd line immunotherapy - B cell depletion | Level U | High | Preferred by experts when pathogenic antibodies are confirmed (+5) |
| Tocilizumab | 2nd line immunotherapy - IL-6 receptor blockade | Level U | High | Increasing frequency of use in adult NORSE (+5) |
| Anakinra | 2nd line immunotherapy - IL-1 receptor antagonism | Level U | Moderate | Mainly used in FIRES (pediatric) (+5) |
| Ketogenic Diet | Neuroprotective effects through ketone body generation | Level U | High | Recommended to start within 1 week in pediatric SRSE (+5) |
| Ketamine | NMDA receptor antagonist | Level U | Moderate | Potential for hallucinations, dissociative symptoms (+4) |
| Therapeutic Hypothermia | Reduced brain metabolic rate and neuroprotective effects | Level U | Very High | Risk of seizure recurrence during rewarming (+5) |
| Surgical Options | Seizure focus removal or seizure propagation interruption | Level U | Very High | Only for cases with clear structural lesions (+5) |
Immunotherapy Timeline and Treatment Strategy
⚠️ EXPERIMENTAL📚 All treatments require latest literature review - Do not make treatment decisions based on this information alone
⏰ Treatment Timeline
0-72H
1st Line Immunotherapy Start: Methylprednisolone, IVIG, or Plasmapheresis
Start immediately when autoimmune/inflammatory cause suspected
1W Later
2nd Line Immunotherapy Consider: Rituximab, Tocilizumab, Anakinra
Start if no response to 1st line treatment
Concurrent
Concurrent Treatment: Ketogenic Diet (pediatric within 1 week), Ketamine, other experimental treatments
Implement concurrently with immunotherapy
🎯 1st Line Immunotherapy Selection Guide
Methylprednisolone: Rapid start, anti-inflammatory
IVIG: Excellent safety, autoantibody neutralization
Plasmapheresis: Rapid effect, severe cases
※ Steroid + IVIG combination or steroid + plasmapheresis combination possible
🔬 2nd Line Immunotherapy Selection Guide
Rituximab: When autoantibodies confirmed, B cell mediated
Tocilizumab: Adult NORSE, IL-6 elevation
Anakinra: FIRES (pediatric), IL-1 mediated
※ Start after evaluating response to 1st line treatment after 1 week
⚠️ Immunotherapy Special Considerations
Essential Tests Before Treatment
- • Neuronal antibody testing (anti-NMDA, anti-LGI1, anti-CASPR2, etc.)
- • Infection screening (bacterial, viral, fungal)
- • Autoimmune disease testing
- • Neuroimaging (MRI, PET)
Monitoring Requirements
- • Infection surveillance (due to immunosuppression)
- • Blood tests (blood count, liver function, kidney function)
- • Immunoglobulin levels
- • Neurological response assessment
Detailed Treatment Information
🧪 ALL EXPERIMENTAL⚠️ All treatments listed below are EXPERIMENTAL
• Always review latest research literature and clinical guidelines
• Do not make treatment decisions without consulting specialists
• Carefully consider individual patient circumstances and risk-benefit ratio
Methylprednisolone
🧪 EXPERIMENTALLevel U Moderate 1st line immunotherapy - Anti-inflammatory
📚 Literature review required - Treatment decisions based on this information alone are prohibited
Dosage & Administration
20-30mg/kg IV (max 1g/day) × 3-5 days
Administration
Start within 24-72 hours of SE onset, gradual tapering
Evidence Summary
Used as 1st line immunotherapy in NORSE/FIRES. Early initiation recommended when autoimmune/inflammatory cause suspected.
Key Considerations
- Recommend starting within 24-72 hours of SE onset
- High dose for 3-5 days then gradual tapering
- Start after infection screening
- Blood glucose elevation and immunosuppressive effects
- Monitor for steroid side effects
- Effective in anti-NMDA receptor encephalitis
IVIG (Immunoglobulin)
🧪 EXPERIMENTALLevel U Moderate 1st line immunotherapy - Autoantibody neutralization
📚 Literature review required - Treatment decisions based on this information alone are prohibited
Dosage & Administration
2g/kg (total dose) / divided over 2-5 days
Administration
Slow infusion (0.5-1g/kg/day), watch for anaphylaxis
Evidence Summary
1st line immunotherapy option. Effective in autoantibody-mediated encephalitis. Can be combined with steroids.
Key Considerations
- Effective in autoantibody-mediated encephalitis
- Thromboembolism risk - slow infusion
- Adequate hydration required
- Can be combined with steroids
- Contraindicated in IgA deficiency
- Renal function monitoring essential
Plasmapheresis
🧪 EXPERIMENTALLevel U High 1st line immunotherapy - Rapid autoantibody removal
📚 Literature review required - Treatment decisions based on this information alone are prohibited
Dosage & Administration
5-7 plasma exchanges (every other day or daily)
Administration
Requires central venous catheter, 1-1.5 plasma volume replacement
Evidence Summary
One of the 1st line immunotherapies. Rapid autoantibody removal. Faster effect than IVIG in severe cases.
Key Considerations
- Faster effect than IVIG in severe cases
- Rapid autoantibody removal possible
- Perform after confirming hemodynamic stability
- Requires technical expertise
- Central venous catheter insertion required
- Coagulation factor supplementation needed
Rituximab
🧪 EXPERIMENTALLevel U High 2nd line immunotherapy - B cell depletion
📚 Literature review required - Treatment decisions based on this information alone are prohibited
Dosage & Administration
375mg/m² weekly × 4 weeks or 1000mg × 2 doses (2 weeks apart)
Administration
Slow infusion, premedication (acetaminophen, antihistamine)
Evidence Summary
2nd line immunotherapy. CD20+ B cell depletion. Preferred by experts when pathogenic antibodies identified.
Key Considerations
- Preferred by experts when pathogenic antibodies are confirmed
- B cell depletion effect, increased risk of infection
- Takes several weeks to take effect
- Risk of hepatitis B reactivation
- Caution for Progressive Multifocal Leukoencephalopathy (PML)
- Long-term immunosuppressive effect
Tocilizumab
🧪 EXPERIMENTALLevel U High 2nd line immunotherapy - IL-6 receptor blockade
📚 Literature review required - Treatment decisions based on this information alone are prohibited
Dosage & Administration
8mg/kg (max 800mg) monthly
Administration
IL-6 receptor antagonist, more commonly used in adults
Evidence Summary
2nd line immunotherapy. Increasing use in adult NORSE. Average 1 week to seizure cessation.
Key Considerations
- Increasing frequency of use in adult NORSE
- Particularly effective with elevated IL-6
- Average seizure cessation within 1 week
- High risk of long-term disability
- Risk of neutropenia
- Liver function monitoring required
Anakinra
🧪 EXPERIMENTALLevel U Moderate 2nd line immunotherapy - IL-1 receptor antagonism
📚 Literature review required - Treatment decisions based on this information alone are prohibited
Dosage & Administration
100mg/day or 1-2mg/kg/day
Administration
IL-1 receptor antagonist, preferred in pediatric FIRES
Evidence Summary
Mainly used in FIRES (pediatric febrile infection-related epilepsy syndrome). Relatively safe profile.
Key Considerations
- Mainly used in FIRES (pediatric)
- Suppresses inflammatory response by blocking IL-1
- Relatively safe immunotherapy
- Risk of neutropenia
- Renal function monitoring required
- Injection site reaction
Ketogenic Diet
🧪 EXPERIMENTALLevel U High Neuroprotective effects through ketone body generation
📚 Literature review required - Treatment decisions based on this information alone are prohibited
Dosage & Administration
Fat:Protein+Carbohydrate = 4:1 ratio
Administration
Enteral nutrition, gradual introduction (3-5 days)
Evidence Summary
Recommended to start within 1 week in pediatric SRSE. Limited case reports in adults. Induces brain metabolic changes through ketosis.
Key Considerations
- Recommended to start within 1 week in pediatric SRSE
- Can be considered in adults as well
- Induces brain metabolic changes through ketosis
- Collaboration with a dietitian is essential
- Takes 24-72 hours to take effect
- Risk of nutritional deficiencies with long-term maintenance
Ketamine
🧪 EXPERIMENTALLevel U Moderate NMDA receptor antagonist
📚 Literature review required - Treatment decisions based on this information alone are prohibited
Dosage & Administration
Loading: 1.5-4.5mg/kg IV, Maintenance: 1-7.5mg/kg/hr
Administration
Loading dose followed by continuous infusion, monitor blood pressure and airway
Evidence Summary
Limited case reports and small retrospective studies. No randomized controlled trials.
Key Considerations
- Potential for hallucinations, dissociative symptoms
- Airway protection needed (intubated state)
- Risk of increased blood pressure
- Relatively safe in hemodynamically stable patients
- Can be tried after failure of other anesthetics
Therapeutic Hypothermia
🧪 EXPERIMENTALLevel U Very High Reduced brain metabolic rate and neuroprotective effects
📚 Literature review required - Treatment decisions based on this information alone are prohibited
Dosage & Administration
Target temperature: 32-34°C
Administration
Intravascular cooling device or surface cooling
Evidence Summary
Some effects reported in small observational studies. Lack of large randomized controlled trials.
Key Considerations
- Risk of seizure recurrence during rewarming
- Increased risk of infection
- Coagulation dysfunction
- Risk of bradycardia and arrhythmias
- Effective temperature control system required
- Complication management is complex
Surgical Options
🧪 EXPERIMENTALLevel U Very High Seizure focus removal or seizure propagation interruption
📚 Literature review required - Treatment decisions based on this information alone are prohibited
Dosage & Administration
Craniotomy, lesionectomy, or hemispherectomy
Administration
Neurosurgical procedure
Evidence Summary
Reported only in very limited cases with structural lesions. No systematic studies.
Key Considerations
- Only for cases with clear structural lesions
- Risk-benefit assessment is essential
- Difficulty of surgery during anesthesia
- Risk of post-surgical neurological deficits
- Very limited indications
- Multidisciplinary team approach required
SRSE Treatment General Principles
Etiological Investigation
Continue systematic examination for autoimmune encephalitis, infectious encephalitis, metabolic causes, toxic causes, etc., and implement specific treatment when a cause is identified.
Multidisciplinary Approach
Collaboration among multidisciplinary teams including neurology, critical care medicine, anesthesiology, clinical pharmacology, and nutrition teams is essential.
Risk-Benefit Assessment
Carefully evaluate the potential benefits and risks of experimental treatments, and make decisions after sufficient consultation with patients and guardians.