What are the detailed classifications of status epilepticus, including time course (early, established, refractory, super‑refractory), clinical type (convulsive versus non‑convulsive with EEG subtypes), underlying etiology (acute symptomatic, remote symptomatic, cryptogenic/idiopathic), pharmacologic response (responsive, refractory, pharmacoresistant), and EEG patterns?

Classification of Status Epilepticus

Status epilepticus is classified along four distinct axes—semiology (clinical type), etiology, EEG correlates, and age—with temporal staging (early, established, refractory, super-refractory) determining treatment escalation and prognosis. 1, 2

Temporal Classification (Time-Based Staging)

The temporal evolution of status epilepticus defines critical treatment thresholds based on two key time points (t1 and t2):

• Early status epilepticus (0–5 minutes): Seizure activity lasting ≥5 minutes, representing the operational threshold when spontaneous termination becomes unlikely and immediate benzodiazepine therapy is mandated 3, 4
• Established status epilepticus (5–20 minutes): Seizures persisting despite first-line benzodiazepine therapy, requiring escalation to second-line intravenous anticonvulsants (phenytoin, valproate, levetiracetam, or phenobarbital) 3, 4
• Refractory status epilepticus (≥20 minutes): Ongoing seizures despite adequate benzodiazepine therapy and failure of one second-line anticonvulsant, necessitating continuous EEG monitoring and anesthetic agents (midazolam, propofol, or pentobarbital) 3, 4
• Super-refractory status epilepticus: Seizures continuing for ≥24 hours after initiation of anesthetic therapy, or recurring during anesthetic wean, representing the most treatment-resistant category with mortality approaching 65% 3, 1

The traditional 30-minute definition has been abandoned because delayed treatment beyond 5 minutes significantly worsens neurological outcomes and mortality (5–22% overall, rising to 65% in refractory cases) 3, 4. Time point t1 (5 minutes) marks when mechanisms responsible for seizure termination fail, while t2 (20–30 minutes) indicates when long-term neuronal injury, network alterations, and cell death become likely 1, 2.

Semiological Classification (Clinical Type)

Convulsive Status Epilepticus

• Generalized convulsive status epilepticus (GCSE): Bilateral tonic-clonic motor activity with impaired consciousness, the most recognizable form requiring immediate intervention 3, 5
• Status epilepticus with prominent motor phenomena (SE-PM): Includes focal motor seizures with or without secondary generalization, myoclonic status, and tonic status 2
• Evolution from convulsive to non-convulsive: Approximately 25% of patients with generalized convulsive status epilepticus develop ongoing non-convulsive electrical seizures after motor manifestations cease, detectable only by continuous EEG 4

Convulsive status epilepticus is surprisingly uncommon in idiopathic generalized epilepsy compared to symptomatic or focal epilepsies, and when it does occur, typically responds rapidly to treatment 6.

Non-Convulsive Status Epilepticus (NCSE)

Non-convulsive status epilepticus cannot be diagnosed by clinical observation alone and requires EEG confirmation, occurring in up to 8% of comatose patients without clinical seizure activity 3. The Salzburg EEG criteria define four subcategories:

• Typical absence status epilepticus: Occurs exclusively in idiopathic generalized epilepsy (IGE) with typical absence seizures and in de novo absence SE of late onset, characterized by continuous spike-wave discharges at 3 Hz with impaired consciousness 2, 6
• Atypical absence status epilepticus: Seen in secondarily generalized epilepsy encephalopathies, with slower spike-wave patterns (<2.5 Hz) and more severe cognitive impairment 2, 6
• Complex partial status epilepticus: Arises from focal epilepsy (temporal or frontal lobe), with focal EEG patterns and fluctuating consciousness 2, 6
• Subtle status epilepticus: Represents the end-stage of prolonged convulsive status epilepticus, with minimal or absent motor manifestations but ongoing electrical seizure activity 5

Clinical clues include subtle motor signs (mouth twitching, digit movements, eyelid twitching), evidence of prior seizures (tongue biting, injuries, incontinence), and persistent altered consciousness without return to baseline 3.

EEG-Based Classification

Electrographic Seizure Patterns

• Electrographic seizure: Any pattern with definite evolution (≥2 unequivocal sequential changes in frequency, morphology, or location) lasting ≥10 seconds, or any pattern with a consistent clinical correlate in lockstep 7
• Electrographic status epilepticus: Any pattern qualifying for electrographic seizure lasting ≥10 continuous minutes, or totaling ≥20% of any 60-minute monitoring period 7
• Electroclinical convulsive status epilepticus: Bilateral tonic-clonic motor activity with corresponding EEG seizure patterns lasting ≥5 continuous minutes 7

Ictal-Interictal Continuum (IIC)

The umbrella term "ictal-interictal continuum" (also termed "possible electrographic status epilepticus") encompasses EEG patterns that fall between clearly ictal and clearly interictal, generated by both the underlying etiology and superimposed epileptic activity 7, 2:

• Periodic discharges or spike/sharp-wave patterns averaging >1.0 and ≤2.5 Hz over 10 seconds 7
• Periodic discharges averaging ≥0.5 Hz and ≤1.0 Hz over 10 seconds with plus modifiers (superimposed fast activity, rhythmic activity, or sharp waves) or fluctuation (≥3 changes in frequency, morphology, or location within 1 minute) 7
• Lateralized rhythmic delta activity averaging >1 Hz over 10 seconds with plus modifiers or fluctuation 7

The contribution of ictal activity in IIC patterns requires diagnostic intravenous ASM trials during EEG recording to assess both EEG and clinical response, supplemented by CT- or MRI-perfusion studies 2.

Etiological Classification

Acute Symptomatic Status Epilepticus

• Metabolic derangements: Hypoglycemia, hyponatremia (the most common electrolyte disturbance precipitating seizures), hypoxia 3, 4
• Acute cerebrovascular events: Ischemic stroke or intracerebral hemorrhage, especially in patients >40 years 4
• Central nervous system infections: Meningitis, encephalitis, brain abscess 3, 4
• Drug toxicity or withdrawal: Alcohol withdrawal, benzodiazepine withdrawal, barbiturate withdrawal, cocaine, amphetamines 3, 4
• Traumatic brain injury: Recent head trauma with structural lesions 4

Acute symptomatic causes account for the majority of status epilepticus cases and require simultaneous identification and correction during anticonvulsant administration 3, 4.

Remote Symptomatic Status Epilepticus

• Prior stroke or hemorrhage: Remote cerebrovascular injury with epileptogenic focus 4
• Traumatic brain injury: Remote head trauma with gliosis or encephalomalacia 4
• Brain tumors: Primary or metastatic malignancies 4
• Developmental abnormalities: Cortical dysplasia, heterotopia 1
• Prior CNS infection: Remote meningitis or encephalitis with residual scarring 1

Cryptogenic/Idiopathic Status Epilepticus

• Idiopathic generalized epilepsy (IGE): Includes juvenile myoclonic epilepsy, childhood absence epilepsy, juvenile absence epilepsy 6
• De novo absence status epilepticus of late onset: Occurs in elderly patients without prior epilepsy history 6
• Unknown etiology: No identifiable structural, metabolic, or genetic cause despite thorough investigation 1

Convulsive status epilepticus is much less common in IGE than in symptomatic epilepsies, and when present, usually responds rapidly to treatment 6.

Pharmacologic Response Classification

Responsive Status Epilepticus

• Benzodiazepine-responsive: Seizures terminating with first-line lorazepam (65% efficacy) or midazolam 4
• Second-line responsive: Seizures controlled with valproate (88% efficacy), levetiracetam (68–73% efficacy), fosphenytoin (84% efficacy), or phenobarbital (58.2% efficacy) 3, 4

Refractory Status Epilepticus

Defined as ongoing seizures despite adequate benzodiazepine therapy and failure of one second-line anticonvulsant, occurring in up to 40% of patients 3, 1. Requires escalation to:

• Midazolam infusion: 80% seizure control rate, 30% hypotension risk 3, 4
• Propofol: 73% seizure control rate, 42% hypotension risk 3, 4
• Pentobarbital: 92% seizure control rate, 77% hypotension risk requiring vasopressors 3, 4

Super-Refractory Status Epilepticus

Seizures persisting ≥24 hours after anesthetic initiation or recurring during anesthetic wean, representing an "almost evidence-free zone" with mortality approaching 65% 3, 1. Fourth-line options include:

• Ketamine: 64% efficacy when administered early (within 3 days), dropping to 32% when delayed to mean 26.5 days 4
• Magnesium, steroids, immunotherapy: Variable outcomes with limited evidence 1

Age-Specific Classification

Pediatric Status Epilepticus

• Febrile status epilepticus: Prolonged febrile seizures in children 6 months to 2 years (affecting 2–4% of children), with antipyretics ineffective for termination or prevention 4
• Myoclonic-astatic epilepsy: Myoclonic status in Doose syndrome 6
• Dravet syndrome: Myoclonic status and prolonged convulsive seizures 6
• Panayiotopoulos syndrome: Autonomic status in 50% of seizures, with focal and generalized features 6
• Electrical status epilepticus in sleep (ESES): Continuous spike-wave discharges during slow-wave sleep 6
• Landau-Kleffner syndrome: Generalized electrographic status with language regression 6

Pediatric dosing differs: lorazepam 0.1 mg/kg IV (max 2 mg) for convulsive SE, 0.05 mg/kg IV (max 1 mg) for non-convulsive SE; levetiracetam loading 40 mg/kg IV (max 2500 mg) 4.

Adult Status Epilepticus

• Idiopathic generalized epilepsy: Typical absence status, myoclonic status in juvenile myoclonic epilepsy, phantom absence with GTCS 6
• Symptomatic epilepsy: Focal SE with or without secondary generalization, representing the majority of adult cases 1
• De novo absence status of late onset: Elderly patients without prior epilepsy, often triggered by medications or metabolic disturbances 6

Neonatal Status Epilepticus

Excluded from this classification system due to distinct pathophysiology, EEG patterns, and treatment algorithms 2.

Special Semiological Subtypes

Myoclonic Status Epilepticus

• In juvenile myoclonic epilepsy: Uncommon but characteristic of IGE 6
• In progressive myoclonic epilepsies: More common, associated with neurodegenerative conditions 6
• Lance-Adams syndrome: Post-hypoxic myoclonus with epileptiform discharges, may be compatible with good outcome and should not be treated overly aggressively 4

Autonomic Status Epilepticus

• Panayiotopoulos syndrome: 50% of seizures qualify as status epilepticus, with prominent autonomic features (vomiting, pallor, incontinence) 6

Generalized Electrographic Status Epilepticus

• Phantom absence with GTCS: Continuous generalized spike-wave discharges without overt clinical manifestations 6
• ESES and Landau-Kleffner syndrome: Continuous spike-wave during sleep with cognitive/language regression 6

Critical Diagnostic Pitfalls

• Neuromuscular blockers mask motor manifestations while allowing continued electrical seizure activity and brain injury—never use rocuronium or other paralytics alone without EEG monitoring 4
• Subtle motor signs require systematic observation: mouth twitching, digit movements, eyelid twitching, nystagmus 3
• Continuous EEG monitoring is essential for detecting non-convulsive seizures in 25% of patients after convulsive activity ceases 4
• IIC patterns require diagnostic ASM trials during EEG recording to distinguish ictal from non-ictal contributions 2
• Post-cardiac arrest myoclonus may be subcortical (not requiring aggressive ASM) versus cortical (requiring treatment)—EEG correlation is mandatory 7