Diagnostic and Classification Criteria in Status Epilepticus
Learning Objective
- Apply diagnostic and classification criteria to assess the severity of status epilepticus (SE) and guide immediate management.
Overview: Status epilepticus is a neurologic emergency defined by seizure duration and response to therapy. Early recognition, targeted diagnostics, and prompt classification drive appropriate pharmacologic escalation and improve outcomes.
1. Operational Definitions and Classification
SE definitions hinge on time thresholds and treatment response. Classification into standard, refractory, and super-refractory SE informs urgency and therapy intensity.
Standard SE:
- Single seizure ≥5 minutes or ≥2 seizures without return to baseline consciousness.
- Rationale: spontaneous cessation unlikely beyond 5 minutes; early benzodiazepine improves cessation rates.
Refractory SE (RSE):
- Ongoing seizures after adequate benzodiazepine (e.g., lorazepam 0.1 mg/kg IV) plus a second‐line Antiseizure Medication (ASM) (fosphenytoin 20 mg PE/kg, valproate 20–40 mg/kg, or levetiracetam 60 mg/kg).
Super-Refractory SE (SRSE):
- SE persisting >24 hours despite continuous anesthetic infusion or recurring on anesthetic wean.
Key Pearl
The 5-minute operational threshold balances the need for early intervention against overtreatment of self-limited seizures.
2. Clinical Examination and Differentiation from Mimics
Differentiate true SE from psychogenic seizures and movement disorders via history, exam, and response to therapy.
A. History:
- Prodrome/aura, witness descriptions, prior epilepsy, ASM adherence, triggers (infection, stroke).
B. Bedside neurologic exam:
- Focal motor signs (unilateral clonic jerking), eye deviation, automatisms, postictal confusion.
C. Psychogenic Non-Epileptic Seizures (PNES):
- Asynchronous/arrhythmic movements, preserved awareness, lack of postictal state, normal EEG during events.
D. Hyperkinetic Movement Disorders:
- Rhythmicity vs arrhythmic, distractible, entrainable limbs, normal EEG.
Case Vignette: A 62-year-old man on the ventilator develops 7 minutes of subtle facial twitching and confusion. Rapid fingerstick glucose is normal; emergent EEG confirms rhythmic epileptiform discharges—initiate benzodiazepine and second-line ASM.
Clinical Pearl
In suspected PNES or movement disorders, absence of EEG seizures despite dramatic movements should prompt reevaluation before ASM escalation.
3. Emergent Laboratory Evaluation
Identify reversible precipitants and optimize ASM selection through targeted labs performed in parallel with initial therapy.
- Metabolic panel: sodium, potassium, calcium, magnesium, glucose
- Renal/hepatic function: creatinine, BUN, AST/ALT, bilirubin
- Toxicology screen: alcohols, illicit drugs, proconvulsant medications
- Infection workup: CBC, CRP/ESR, blood cultures, CSF analysis if fever or meningeal signs
- ASM levels: phenytoin, valproate, carbamazepine in known epileptics
| ASM | Therapeutic Range | Toxic Level | Notes |
|---|---|---|---|
| Phenytoin | 10-20 mcg/mL | >30 mcg/mL | Monitor free level if albumin low; highly protein-bound. |
| Valproate | 50-100 mcg/mL | >150 mcg/mL | Check ammonia if encephalopathy develops. |
| Carbamazepine | 4-12 mcg/mL | >15 mcg/mL | Autoinducer; monitor for drug interactions. |
| Levetiracetam | (Not routinely monitored) | N/A | Dose adjust for renal impairment; generally well-tolerated. |
| Phenobarbital | 15-40 mcg/mL | >50 mcg/mL | Significant sedation; respiratory depression risk. |
Key Pearl
Do not delay benzodiazepine administration to await laboratory results—correct reversible causes concurrently.
4. Neuroimaging in SE
Early imaging defines structural etiologies that may alter management.
- Noncontrast head CT (emergent): rule out hemorrhage, mass effect—perform at bedside if unstable.
- Brain MRI (DWI/FLAIR): detect ischemia, inflammation, subtle lesions once patient stabilized.
- Vascular imaging (CTA/MRA): indicated when stroke suspected; perfusion studies for salvageable tissue.
Imaging Algorithm:
Neuroimaging Algorithm in SE
Clinical Pearl
While CT is rapid and widely available, MRI may reveal encephalitis or small infarcts critical for targeted therapy.
5. Electroencephalographic Monitoring
EEG is essential for diagnosing nonconvulsive SE (NCSE) and guiding treatment titration in RSE/SRSE.
A. Indications:
- Persistent altered mental status after convulsions.
- Suspected NCSE or RSE.
B. Modalities:
- Rapid (20-minute) EEG vs continuous EEG (cEEG).
- Recommended 24–48 hours of cEEG in high-risk patients.
C. Key EEG patterns:
- Periodic lateralized epileptiform discharges (PLEDs).
- Rhythmic delta activity, epileptiform discharges >2.5 Hz (Salzburg criteria).
D. Therapeutic endpoints:
- Electrographic seizure suppression or burst suppression to guide anesthetic infusions.
Key Pearl
cEEG uncovers seizures in ~15–20% of critically ill patients with unexplained encephalopathy; informs escalation and weaning of therapy.
6. Integrated Diagnostic Algorithm
A protocol-driven sequence ensures timely classification and management.
Integrated Diagnostic Algorithm for Status Epilepticus
7. Pearls, Pitfalls, and Controversies
A. Clinical Pearls & Pitfalls:
- Pearl: Under-recognition of NCSE delays treatment—cEEG is critical in patients with unexplained altered mental status after convulsive SE or in those at high risk.
- Pitfall: Over-reliance on CT may miss encephalitis or small infarcts—pursue MRI when clinically indicated and safe to do so.
- Pearl: Early and aggressive treatment of SE is associated with better outcomes; “time is brain.”
- Pitfall: Inadequate dosing of initial benzodiazepines or second-line ASMs can lead to pseudo-refractoriness. Ensure weight-based, appropriate doses are administered.
B. Key Controversies and Evolving Definitions:
Evolving Definitions & Thresholds
The operational definition of SE (typically 5 minutes for generalized convulsive SE) continues to be discussed. Some debate whether a 10-minute threshold might be more appropriate for certain SE types or to avoid overtreatment, though current guidelines emphasize early intervention.
cEEG Resource Utilization
Continuous EEG (cEEG) is resource-intensive (equipment, personnel for interpretation). Balancing its high diagnostic yield in detecting NCSE and guiding therapy against these constraints is an ongoing challenge. Standardization of cEEG initiation criteria and minimum duration of monitoring are areas of active discussion and research.
Impact of cEEG on Long-Term Outcomes
While cEEG clearly improves detection of non-convulsive seizures and can guide acute therapy, robust evidence demonstrating a direct impact on long-term neurological outcomes or mortality is still evolving. Further research is needed to solidify its role in improving patient-centered long-term results beyond immediate seizure control.
References
- Trinka E, Cock H, Hesdorffer D, et al. A definition and classification of status epilepticus—report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia. 2015;56(10):1515–1523.
- Glauser T, Shinnar S, Gloss D, et al. Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus in Children and Adults. Epilepsy Currents. 2016;16(1):48–61.
- Brophy GM, Bell R, Claassen J, et al. Guidelines for the Evaluation and Management of Status Epilepticus. Neurocrit Care. 2012;17(1):123–134.
- Riviello JJ Jr, Ashwal S, Hirtz D, et al. Practice parameter: Diagnostic assessment of the child with status epilepticus. Neurology. 2006;67(9):1542–1550.
- Leitinger M, Beniczky S, Rohracher A, et al. Salzburg consensus criteria for non-convulsive status epilepticus. Epilepsy Behav. 2015;49:158–163.
- Rossetti AO, Schindler K, Sutter R, et al. Continuous vs routine electroencephalogram in critically ill adults with altered consciousness. JAMA Neurol. 2020;77(10):1225–1233.
- Claassen J, Hirsch LJ, Emerson RG, Bates JE, Thompson TB, Mayer SA. Continuous EEG monitoring and midazolam infusion for refractory nonconvulsive status epilepticus. Neurology. 2001;57(6):1036–1042.
- Gaspard N, Foreman B, Judd LM, et al. Intravenous ketamine for refractory status epilepticus: a retrospective multicenter study. Epilepsia. 2013;54(8):1498–1503.
