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Mechanistic Deep Dive
Pathophysiology of SE
- Initial: imbalance of excitation/inhibition
- Sustained: receptor trafficking changes
- GABA-A receptors internalized (BZD-resistant)
- NMDA receptors externalized (excitotoxicity)
- Excitotoxic neuronal injury (calcium-mediated)
- Apoptosis + necrosis
- Long-term: neuronal loss, gliosis, epileptogenesis
Why Treat Early
- BZDs less effective after 30-60 min (receptor changes)
- Refractoriness develops with time
- Permanent injury occurs
Recent Trials & Updates
ESETT (2019)
- Established Status Epilepticus Treatment Trial
- 3-arm RCT: fosphenytoin vs valproate vs levetiracetam
- All ~ 50% effective
- Practitioner choice based on availability + comorbidities
RAMPART (2012)
- IM midazolam vs IV lorazepam in pre-hospital
- IM midazolam non-inferior
- Useful when IV access difficult
KETASER01 (2023)
- Ketamine vs midazolam in refractory SE
- Ketamine non-inferior
Brivaracetam IV
- Faster onset than levetiracetam
- May replace in protocols
- FDA-approved adjunct
Lacosamide for SE
- Added in some protocols
- Available IV
- PR prolongation caveat
High-Yield Specialist Points
Subtle CSE
- After prolonged convulsive activity
- Minor motor activity (eyelid, facial twitches)
- Coma
- Continuous electrical activity
- Easy to miss
- Treat aggressively
NORSE (New-Onset Refractory SE)
- Previously healthy patients
- Refractory SE
- No identified cause initially
- Often autoimmune (anti-NMDA-R, anti-LGI1, others)
- Immunotherapy crucial
- Often need multiple agents
- Ketogenic, anakinra (IL-1 inhibitor for FIRES)
Pyridoxine for INH Toxicity
- Pyridoxine 1:1 with INH ingested
- Empiric 5 g IV if dose unknown
- Treats both seizures and acidosis
Theophylline Toxicity
- Refractory seizures
- Treatment: BZDs, phenobarbital (not phenytoin)
- Charcoal hemoperfusion + HD
- Severe = level > 100 ÎŒg/mL
Bupropion Overdose
- Seizures common
- Treatment: BZDs, supportive
Cefepime-Induced Encephalopathy
- NCSE
- Renal impairment common
- Discontinue cefepime + dialysis
Local Anesthetic Toxicity
- Bupivacaine cardiotoxic + seizures
- Lipid emulsion 20% rescue
Pseudo-Status (PNES)
- Psychogenic
- May mimic SE
- Video-EEG diagnostic
- Avoid intubation/anesthesia if just PNES
- But unclear â treat as SE while obtaining EEG
Convulsive Syncope
- Brief jerks during syncope
- Different from SE
- Cardiac workup
Pearls
- SE = ⥠5 min or ⥠2 without recovery
- Staged treatment (BZD â ESETT ASM â anesthesia â super-refractory)
- BZDs more effective early (receptor trafficking)
- ESETT 2019: levetiracetam, fosphenytoin, valproate all comparable second-line
- Anesthesia for refractory: midazolam, propofol, pentobarbital
- cEEG essential after anesthesia + for NCSE
- NCSE common in ICU comatose (8-37%)
- Mortality 10-20% overall; refractory 30-50%; super-refractory > 50%
- NORSE/FIRES: often autoimmune, immunotherapy + anakinra
- Eclampsia: magnesium sulfate + delivery
- Anti-NMDA-R: immunotherapy + tumor search