Nervous System & Special Senses

Status epilepticus: CCS-style management

Clinical Overview and When to Suspect Status Epilepticus

— t1 (when to treat as SE): ≥5 minutes of continuous convulsive activity, or ≥2 seizures without return to baseline

— t2 (when long-term consequences begin): ≥30 minutes — neuronal injury, pharmacoresistance

— Convulsive SE (CSE): generalized tonic-clonic, most common ED presentation, true neurologic emergency

— Nonconvulsive SE (NCSE): altered mental status without motor activity; suspect in any persistent unexplained encephalopathy, especially post-CSE "subtle SE"

— Focal SE with/without impaired awareness

— Witnessed generalized convulsion lasting >5 min, or recurrent seizures in ED

— Postictal patient who fails to wake within 20–30 min — must rule out NCSE with EEG

— ICU patient with unexplained coma, subtle facial/eye twitching, or rhythmic nystagmus

— Known epileptic with abrupt AED noncompliance, infection, or new metabolic derangement

— Acute symptomatic: stroke, CNS infection, TBI, hypoglycemia, hyponatremia, hypocalcemia, uremia, hepatic failure, eclampsia, drug toxicity (cocaine, TCA, bupropion, INH), alcohol/benzodiazepine withdrawal

— Remote symptomatic: prior stroke, neurodegenerative disease, old TBI

— Idiopathic/cryptogenic: AED nonadherence is the #1 cause in known epileptics

CCS pearl: On the CCS, the clock starts the moment you write "patient seizing." Do not wait — order fingerstick glucose, IV access, O2, pulse ox, cardiac monitor, and IV lorazepam simultaneously on the first screen. Delay >10 min to first benzodiazepine is the single most common scoring deduction.

Definition (operational, ILAE 2015): Status epilepticus (SE) is a seizure that fails to terminate or recurs without recovery between events.

Classification:

When to suspect on the CCS case:

Etiology buckets (drive your CCS orders):

Mortality: 20% overall; rises to 30–50% in refractory SE and >50% in super-refractory SE (>24h despite anesthetics).

Presentation Patterns and Key History

— Generalized tonic-clonic movements, eyes deviated/rolled up, frothing, tongue biting (lateral > tip), urinary incontinence

— Cyanosis from apnea during tonic phase, then deep irregular breathing

— Postictal Todd paralysis can mimic stroke — focal weakness resolving over hours

— Persistent confusion, aphasia, staring, automatisms (lip-smacking, picking)

— Subtle motor signs: facial twitching, finger jerks, rhythmic eye deviation, nystagmoid jerks

— Coma without clear cause after CSE — assume NCSE until EEG proves otherwise

— Seizure semiology: onset (focal vs generalized), duration, # of episodes, return to baseline?

— Last known well: anchors stroke vs seizure differential

— Epilepsy history: AED list, last dose, recent dose changes, drug levels checked recently

— Triggers: sleep deprivation, alcohol binge or withdrawal (typically 6–48h after last drink), infection, missed dialysis, recent neurosurgery

— Toxic exposures: cocaine, methamphetamine, tramadol, bupropion, isoniazid (give pyridoxine), TCAs, organophosphates

— Pregnancy status: eclampsia until proven otherwise in 2nd half of pregnancy or up to 6 weeks postpartum

— Comorbidities: DM (hypoglycemia), CKD/ESRD, liver disease, HIV (CNS infection/mass)

— First-ever seizure age >40, focal onset, fever, headache, immunocompromise, head trauma, anticoagulation

Board pearl: A "seizure" lasting >5 minutes by witness account = status epilepticus. Do not wait for 30 minutes — the operational threshold for treatment is 5 minutes because spontaneous termination becomes unlikely and neuronal injury accumulates.

Key distinction: Syncope with convulsive jerks (convulsive syncope) is brief (<15 sec), no postictal confusion, often vasovagal trigger — do not load with AEDs.

Classic convulsive SE presentation:

Nonconvulsive SE — easy to miss:

Focused history (obtain from EMS, family, bystanders while treating):

Red-flag features signaling structural/infectious cause:

Physical Exam Findings and Hemodynamic Assessment

— Airway: position patient lateral decubitus, jaw thrust, nasal trumpet, suction secretions; avoid forcing objects between teeth

— Breathing: assess chest rise, RR, SpO₂; apnea common during tonic phase and after benzodiazepines — be ready to bag-mask

— Circulation: HR, BP, perfusion; sympathetic surge causes early HTN and tachycardia, late hypotension signals decompensation or drug effect

— Note lateralization: version of head/eyes, focal limb predominance → suggests focal-onset seizure with structural lesion

— Pupils: dilated, often unreactive mid-seizure; pinpoint pupils suggest opioid or organophosphate toxicity

— Posturing vs seizing: decerebrate/decorticate posturing is not seizure — think herniation

— GCS, pupillary response, fundoscopy (papilledema → ↑ICP)

— Tongue laceration (lateral bite is specific), shoulder dislocation, posterior shoulder injury, vertebral compression fracture

— Todd paralysis: focal weakness resolving within 24h (usually <1h)

— Persistent coma >20–30 min after motor activity stops → assume NCSE, get stat EEG

— Phase 1 (compensated, <30 min): ↑BP, ↑HR, ↑glucose, ↑lactate, hyperthermia

— Phase 2 (decompensated, >30 min): hypotension, hypoglycemia, hypoxia, rhabdomyolysis, cerebral autoregulation fails → ischemic injury

— Fever + meningismus → CNS infection

— Needle tracks → toxicologic

— Gravid uterus → eclampsia

— AV fistula → uremia

— Stigmata of chronic liver disease → hepatic encephalopathy/hyponatremia

Step 3 management: If hyperthermia >38.5°C develops during prolonged SE, treat actively with cooling measures and acetaminophen — hyperthermia accelerates neuronal injury independent of seizure activity. Do not assume infection until cultures return.

Initial ABC-focused exam (parallel with benzodiazepine administration):

Neurologic exam during seizure:

Postictal exam (when movements stop):

Hemodynamic phases of SE:

Look for etiologic clues:

Diagnostic Workup — Initial Labs, Imaging, ECG

— Fingerstick glucose — the fastest, cheapest, most important test; if <60 mg/dL or unknown, give thiamine 100 mg IV then D50 50 mL IV

— CBC, BMP (Na, Ca, Mg, BUN/Cr, glucose), LFTs, CK (rhabdomyolysis), lactate (often elevated, normalizes within 1h post-seizure — high lactate that doesn't clear suggests ongoing seizure or sepsis)

— Toxicology: urine drug screen, serum alcohol, acetaminophen, salicylate level

— AED levels if known epileptic: phenytoin, valproate, levetiracetam, carbamazepine, phenobarbital

— Pregnancy test (β-hCG) in all women of reproductive age

— ABG if persistent altered mental status or hypoxia

— Blood cultures, lactate, procalcitonin if febrile

— Rule out long QT (torsades can mimic seizure), Brugada, ischemia

— Avoid IV phenytoin/fosphenytoin in 2nd/3rd-degree block, severe bradycardia

— Non-contrast head CT for all first-time seizures, focal features, trauma, anticoagulation, immunocompromised, persistent altered mental status, or failure to return to baseline

— Obtain after seizure is controlled — never transport an actively seizing patient

— MRI brain more sensitive for ischemic stroke, encephalitis, tumor, cortical dysplasia — order on admission, not in ED

— Indicated if fever, meningismus, immunocompromise, or suspected SAH with negative CT

— Check INR/platelets first; CT before LP if focal deficits, papilledema, immunocompromise, or altered mentation

CCS pearl: A common scoring trap — ordering head CT before stabilizing airway and controlling seizure. Sequence: benzodiazepine → glucose → labs → second-line AED → then imaging once stable.

Key distinction: Post-ictal lactic acidosis clears within 60–90 minutes; persistent lactate >4 mmol/L suggests ongoing seizure (possibly NCSE) or sepsis — get EEG.

Order simultaneously with first benzodiazepine (CCS: all on first screen):

ECG:

Imaging:

Lumbar puncture:

Diagnostic Workup — EEG and Advanced Studies

— Indications:

— Persistent altered consciousness >20–30 min after motor activity stops (rule out NCSE)

— Refractory SE requiring anesthetic infusion (titrate to burst suppression)

— Comatose ICU patients with unexplained encephalopathy

— Subtle motor signs (eye deviation, facial twitching) raising NCSE suspicion

— Duration: minimum 24 hours in comatose patients; 48 hours if prior seizures; longer if anesthetic infusions running

— Targets in refractory SE: seizure suppression preferred; burst suppression (10–20s interburst interval) for super-refractory cases

— Identifies structural lesions: stroke, tumor, abscess, cortical dysplasia, mesial temporal sclerosis, PRES, autoimmune encephalitis

— DWI restriction in cortex/hippocampus can be peri-ictal change — mimics stroke; repeat imaging clarifies

— Add MRV if suspecting cerebral venous sinus thrombosis (postpartum, hypercoagulable, OCP use)

— Cell count, glucose, protein, Gram stain, culture, HSV PCR, VZV PCR, cryptococcal antigen if immunocompromised

— Autoimmune encephalitis panel (anti-NMDA, anti-LGI1, anti-CASPR2, anti-GABA-B) — increasingly tested; consider in young patients with psychiatric prodrome and refractory SE

— Ammonia (valproate use, hepatic failure)

— TSH, cortisol if endocrinopathy suspected

— Heavy metals, porphyrins if exposure history

— HIV testing in all first-presentation SE without clear cause

Board pearl: New-onset refractory status epilepticus (NORSE) in a previously healthy adult should trigger workup for autoimmune/paraneoplastic encephalitis (anti-NMDA, especially with ovarian teratoma in young women) and infectious causes. Empiric immunotherapy (steroids, IVIG, plasma exchange) is often started while awaiting antibodies.

Continuous EEG (cEEG) — the cornerstone of advanced SE workup:

MRI brain (with and without contrast, plus DWI):

Lumbar puncture (post-stabilization):

Targeted additional workup:

Management Logic — The SE Timeline

— 0–5 min — Stabilization phase:

— ABCs, position, suction, O₂, IV access ×2, fingerstick glucose, monitor, EKG

— Time the seizure from witness onset

— Begin focused history collection from family/EMS

— 5–20 min — Initial therapy (first-line benzodiazepines):

— IV lorazepam 0.1 mg/kg (max 4 mg/dose) — preferred

— IM midazolam 10 mg if no IV access (≥40 kg) — equivalent efficacy per RAMPART trial

— IV diazepam 0.15–0.2 mg/kg (max 10 mg/dose) alternative

— May repeat once at 5 minutes if seizure persists

— 20–40 min — Second-line therapy (urgent control AED):

— Levetiracetam 60 mg/kg IV (max 4.5 g) — first choice; no drug interactions, safe in hepatic disease

— Fosphenytoin 20 mg PE/kg IV (or phenytoin 20 mg/kg) — monitor BP, ECG, avoid in heart block

— Valproate 40 mg/kg IV (max 3 g) — avoid in pregnancy, hepatic disease, mitochondrial disorders, urea cycle defects

— ESETT trial: all three roughly equivalent (~45% efficacy)

— 40–60 min — Refractory SE — anesthetic infusion:

— Intubate, transfer ICU, start midazolam, propofol, or pentobarbital continuous infusion

— Continuous EEG monitoring titrated to seizure suppression or burst suppression

— >24 h despite anesthetics — Super-refractory SE:

— Add ketamine, immunotherapy if NORSE, ketogenic diet, consider lacosamide/topiramate

CCS pearl: On the CCS clock, write "lorazepam 4 mg IV" at minute 0, repeat at 5 min if still seizing, then levetiracetam 60 mg/kg IV at minute 10–15. Failure to escalate within 20 min loses points.

Step 3 management: Do NOT underdose benzodiazepines — inadequate first-dose benzodiazepine is the most common preventable cause of refractory SE.

Time-based algorithm (Neurocritical Care Society / AES 2016, updated):

Pharmacotherapy — First-Line and Urgent-Control Agents

— Lorazepam IV: 0.1 mg/kg, typically 4 mg, may repeat ×1 after 5 min. Onset 2–3 min; duration 12–24h. Preferred when IV available.

— Midazolam IM: 10 mg single dose for ≥40 kg (5 mg if <40 kg). Onset 3–5 min. Use when IV access delayed (RAMPART trial: noninferior to IV lorazepam, often faster).

— Midazolam intranasal/buccal: 0.2 mg/kg — useful in pediatrics and prehospital

— Diazepam IV: 0.15–0.2 mg/kg, max 10 mg. Short CNS duration (redistributes) — needs follow-on AED

— Diazepam rectal: 0.2–0.5 mg/kg — home/prehospital use

— Adverse effects: respiratory depression, hypotension, paradoxical agitation; have BVM ready

— Levetiracetam (Keppra): 60 mg/kg IV over 10 min (max 4.5 g). No drug interactions, no hepatic metabolism, dose-reduce in CKD (CrCl <50). Best safety profile — frequently first choice.

— Fosphenytoin: 20 mg PE/kg IV at ≤150 mg PE/min. Monitor BP and ECG continuously. Avoid: 2nd/3rd-degree AV block, sinus bradycardia, Brugada, hemodynamic instability. Causes purple glove syndrome (less than phenytoin).

— Phenytoin: 20 mg/kg IV at ≤50 mg/min. Must go through filter, only in normal saline (precipitates in D5W). Extravasation → tissue necrosis.

— Valproate: 40 mg/kg IV over 10 min (max 3 g). Avoid: pregnancy (teratogenic — neural tube defects), hepatic dysfunction, urea cycle disorders, mitochondrial disease (Alpers syndrome in children). Causes hyperammonemia.

— Lacosamide: 200–400 mg IV over 15 min. Useful adjunct; PR-interval prolongation risk

— Phenobarbital: 15–20 mg/kg IV at ≤50–100 mg/min. Causes profound sedation, hypotension; useful when others contraindicated

Board pearl: Isoniazid (INH) overdose seizures are refractory to benzodiazepines alone — give pyridoxine (vitamin B6) 5 g IV (or gram-for-gram INH ingested). Tested repeatedly.

First-line: Benzodiazepines (GABA-A potentiation)

Second-line (urgent control AED) — give even if seizures stop, to prevent recurrence:

Refractory and Super-Refractory SE — Anesthetic Infusions and Escalation

— Midazolam infusion: loading 0.2 mg/kg, then 0.05–2 mg/kg/h. First-line in most US ICUs. Tachyphylaxis common after 24–48h.

— Propofol infusion: loading 1–2 mg/kg, then 30–200 mcg/kg/min. Watch for propofol infusion syndrome (rhabdomyolysis, metabolic acidosis, cardiac failure) — limit to <80 mcg/kg/min for prolonged use; monitor CK, lactate, triglycerides.

— Pentobarbital: loading 5–15 mg/kg, then 0.5–5 mg/kg/h. Reserved for failures of above; causes profound hypotension (often needs pressors), ileus, prolonged emergence.

— Ketamine: loading 1.5–3 mg/kg, then 1–10 mg/kg/h. NMDA antagonist — increasingly used in super-refractory SE; preserves hemodynamics. Watch for hypertension, increased secretions.

— Maintain seizure suppression × 24–48 hours

— Then taper slowly while monitoring cEEG; if seizures recur, return to higher dose ×24h more

— Continue maintenance AEDs throughout (levetiracetam + valproate or fosphenytoin)

— Add second/third AED (lacosamide, topiramate, perampanel)

— Ketogenic diet via NG

— Immunotherapy if NORSE: high-dose methylprednisolone, IVIG, plasma exchange, rituximab

— Therapeutic hypothermia (32–35°C) — investigational

— Inhaled anesthetics (isoflurane) — last resort

— Mechanical ventilation, vasopressors for hypotension, treat hyperthermia, NG tube for AEDs

— Rhabdomyolysis: aggressive IV fluids, monitor CK, urine output, K+

— DVT prophylaxis (mechanical initially, then chemical)

— Aspiration pneumonia surveillance

CCS pearl: Once you intubate for SE, advance the clock to ICU, order continuous EEG, midazolam drip, and levetiracetam maintenance, and consult neurology and neurocritical care — all in one screen.

Refractory SE (RSE): seizures continuing despite adequate first-line benzo + one second-line AED (~30–40% of cases). Action: intubate, ICU, continuous EEG, anesthetic infusion.

Anesthetic agents (titrate to seizure suppression or burst suppression on cEEG):

Anesthetic strategy:

Super-refractory SE (>24h despite anesthetics) — mortality >50%:

Supportive ICU care:

Special Populations — Elderly and Renal/Hepatic Impairment

— SE incidence highest at extremes of age; in elderly, often acute symptomatic (stroke is #1 cause, then metabolic, then dementia-related)

— Lower physiologic reserve — respiratory depression, hypotension, delirium more common with benzodiazepines

— Reduce initial doses by ~25% but do not underdose first benzo — inadequate dosing prolongs SE

— Polypharmacy interactions: warfarin (phenytoin/valproate displace it), DOACs (phenytoin/carbamazepine reduce levels), digoxin

— Falls risk from sedation post-event; deconditioning during hospitalization

— Levetiracetam: strongly renally cleared — dose-adjust:

— CrCl 50–80: 1000–2000 mg q12h

— CrCl 30–50: 750–1500 mg q12h

— CrCl <30: 500–1000 mg q12h

— Hemodialysis: 500–1000 mg q24h plus 250–500 mg post-dialysis supplement

— Lacosamide: reduce by 25% if CrCl <30

— Phenytoin: highly protein-bound — in uremia, free fraction rises; total levels misleading. Check free phenytoin level (target 1–2 mcg/mL).

— Valproate: similar protein-binding issue; check free valproate

— Dialysis can precipitate seizures via dysequilibrium syndrome, hyponatremia, or removal of AEDs (levetiracetam, gabapentin, topiramate are dialyzable)

— Avoid valproate (hepatotoxicity, hyperammonemia, can precipitate hepatic encephalopathy)

— Avoid phenytoin if severe dysfunction (hepatic metabolism, altered protein binding)

— Preferred: levetiracetam, lacosamide — minimal hepatic metabolism

— Phenobarbital: hepatically metabolized but acceptable in moderate disease

Step 3 management: In an elderly patient with new SE and no prior epilepsy history, order stat non-contrast head CT once stabilized — ischemic stroke and intracerebral hemorrhage cause ~30–40% of new-onset SE in this group, and management diverges sharply (thrombolysis window, BP control, neurosurgery).

Key distinction: Always check a free (unbound) phenytoin level in CKD or hypoalbuminemia — total levels falsely reassure or alarm.

Elderly considerations:

Renal impairment:

Hepatic impairment:

Special Populations — Pregnancy, Pediatrics, and Eclampsia

— New-onset seizure in 2nd half of pregnancy or up to 6 weeks postpartum = eclampsia until proven otherwise

— First-line: magnesium sulfate 4–6 g IV loading over 15–20 min, then 1–2 g/h infusion

— Monitor for Mg toxicity: loss of deep tendon reflexes (first sign), respiratory depression, cardiac arrest; antidote calcium gluconate 1 g IV

— Definitive treatment: delivery

— Control severe hypertension: labetalol IV or hydralazine IV; target SBP <160 / DBP <110

— For epilepsy unrelated to eclampsia: benzodiazepines first-line, then levetiracetam preferred (best pregnancy safety profile)

— AVOID valproate (neural tube defects, decreased IQ — Category X for migraine, high-risk for epilepsy when alternatives exist)

— AVOID phenytoin if possible (fetal hydantoin syndrome, cleft lip/palate, cardiac defects)

— Folate 4 mg/day for all women on AEDs planning pregnancy

— First-line: IV lorazepam 0.1 mg/kg, or IM/IN midazolam 0.2 mg/kg, or rectal diazepam 0.5 mg/kg

— Second-line: levetiracetam 60 mg/kg IV or fosphenytoin 20 mg PE/kg

— Common etiologies: febrile SE (>5 min febrile seizure), CNS infection, inborn errors of metabolism, trauma (consider NAT)

— Pyridoxine 100 mg IV for any neonate (<1 month) with refractory SE — pyridoxine-dependent epilepsy

— Glucose: neonatal hypoglycemia uses D10W 2 mL/kg, not D50

— All AEDs reduce OCP efficacy variably (enzyme-inducers especially: phenytoin, carbamazepine, topiramate >200 mg, phenobarbital); use higher-dose OCP, IUD, or barrier

— Levetiracetam and lacosamide do not significantly affect OCPs

— Preconception counseling: switch to least teratogenic agent (lamotrigine, levetiracetam) ≥6 months before conception

Board pearl: A postpartum woman with new seizure — think eclampsia (give magnesium), cerebral venous sinus thrombosis (MRV), posterior reversible encephalopathy syndrome (PRES), or pituitary apoplexy (Sheehan). CT first; MRI/MRV for completeness.

Pregnancy and eclampsia:

Pediatric SE:

Women of reproductive age — chronic AED counseling:

Complications and Adverse Outcomes

— Neuronal injury from glutamate excitotoxicity, mitochondrial failure — duration-dependent

— Cerebral edema and ↑ICP in prolonged SE

— Cognitive sequelae: memory deficits, executive dysfunction, especially after RSE

— Subsequent epilepsy in 20–40% of first-time SE patients

— Mortality: 10% (CSE), 20–30% (RSE), >50% (super-RSE)

— Aspiration pneumonia — most common acute complication (up to 30%)

— Neurogenic pulmonary edema in prolonged SE

— Respiratory failure from medications or seizure itself

— Hypoxic brain injury if airway not protected

— Sympathetic surge → demand ischemia, troponin leak, Takotsubo cardiomyopathy

— Late hypotension from medications (propofol, pentobarbital, phenytoin)

— Arrhythmias: phenytoin-induced bradycardia/heart block; QT prolongation

— Lactic acidosis (usually clears in 60–90 min)

— Rhabdomyolysis → AKI; monitor CK, urine output, K+; aggressive IV fluids

— Hyperthermia from sustained muscle activity (>40°C possible)

— Hyperglycemia early, hypoglycemia late

— Posterior shoulder dislocation (classic), vertebral compression fractures, tongue laceration, dental trauma, head injury from fall

— Propofol infusion syndrome (PRIS): metabolic acidosis, rhabdomyolysis, hypertriglyceridemia, cardiac failure — limit >48h or >80 mcg/kg/min

— Phenytoin extravasation → purple glove syndrome (limb ischemia)

— Valproate-induced hyperammonemia, pancreatitis, thrombocytopenia

— Levetiracetam: behavioral changes, suicidal ideation

— Ventilator-associated pneumonia, line infections, DVT/PE in prolonged ICU stay

CCS pearl: Always order CK and urine myoglobin within 6 hours of SE termination. If CK >5000 or rising, start isotonic IV fluids at 1.5× maintenance targeting urine output 200–300 mL/h to prevent pigment nephropathy.

Key distinction: A troponin rise post-SE is usually demand ischemia (type 2 MI), not plaque rupture — but obtain ECG and serial troponins; if dynamic changes or persistent chest pain, consult cardiology.

Neurologic:

Respiratory:

Cardiovascular:

Metabolic:

Traumatic:

Iatrogenic:

When to Escalate Care — ICU, Consults, and Disposition

— Refractory SE requiring anesthetic infusion

— Intubated for airway protection or respiratory failure

— Persistent altered mental status with concern for NCSE

— Hemodynamic instability or vasopressor requirement

— Severe rhabdomyolysis (CK >5000) with AKI risk

— Underlying acute neurologic emergency (stroke, ICH, meningitis, encephalitis)

— Eclampsia requiring active magnesium and BP titration

— SE that responded to benzodiazepine + one urgent-control AED, fully awake, hemodynamically stable

— Continuous cardiac monitoring × 24h

— Telemetry if phenytoin/fosphenytoin/lacosamide given

— Known epileptic with breakthrough seizure from missed dose, fully recovered, back to baseline AED, no other concerning features

— Neurology: all SE cases — for AED selection, cEEG interpretation, post-SE planning

— Neurocritical care: RSE/super-RSE

— Neurosurgery: if structural lesion (hemorrhage, mass, hydrocephalus, severe TBI)

— Infectious disease: suspected CNS infection or immunocompromise

— OB: any pregnancy-related SE

— Toxicology/poison control: suspected overdose

— Cardiology: for troponin elevation, arrhythmia, Takotsubo

— Known epileptic, single brief seizure (not SE), returned to baseline, reliable caregiver, AED adjustment plan, neurology follow-up within 1–2 weeks

— Otherwise, admit for first-time SE, prolonged seizure, unclear etiology, or social concerns

Step 3 management: Even after seizures stop, continue cEEG for ≥24 hours in any patient who does not return to neurologic baseline within 30–60 minutes — undetected NCSE prolongs ICU stay and worsens outcomes. This is a recurring Step 3 vignette.

ICU admission criteria (admit all of these):

Step-down or monitored unit (most non-refractory cases):

Floor admission acceptable:

Consultations:

Discharge from ED — only if ALL of:

Key Differentials — Same-Category (Other Seizure-Like Events)

— Single brief seizure (<5 min) with full recovery: not SE; observation, etiology workup, outpatient neurology if first-ever

— Cluster seizures: ≥2 seizures within 24h with recovery between — high risk of progression to SE; load with AED but not anesthetics

— Acute repetitive seizures: treated with home rescue benzodiazepine (rectal diazepam, intranasal midazolam, buccal midazolam)

— Focal SE without impaired awareness (epilepsia partialis continua): continuous focal motor jerks, preserved consciousness; treat aggressively but avoid intubation if not needed

— Absence SE (typical/atypical): prolonged confusional state with generalized 3-Hz or atypical spike-wave on EEG; treat with IV benzodiazepine + valproate or levetiracetam; avoid phenytoin (can worsen)

— Myoclonic SE: rhythmic myoclonic jerks; consider post-anoxic (poor prognosis after cardiac arrest), juvenile myoclonic epilepsy, or toxic-metabolic

— Nonconvulsive SE: altered mental status + electrographic seizures on EEG; needs EEG to diagnose

— Convulsive vs nonconvulsive: motor activity present vs absent; both require equally aggressive treatment

— Generalized vs focal onset: focal → look for structural lesion (image first)

— Absence vs complex partial: absence ends abruptly with no postictal confusion; complex partial has automatisms and postictal haze

Board pearl: Post-cardiac-arrest myoclonic SE within 24 hours of ROSC traditionally portended poor prognosis, but early myoclonus alone is no longer a definitive predictor; obtain cEEG, SSEPs, neuron-specific enolase, MRI — multimodal prognostication after ≥72 hours off sedation per AAN guidelines.

Key distinction: Absence SE can mimic NCSE in elderly with confusion — EEG distinguishes; treat with benzo + valproate/levetiracetam, NOT phenytoin or carbamazepine (which worsen generalized epilepsies).

Within the seizure family — distinguish before committing to SE pathway:

Distinguishing features (key on stems):

Key Differentials — Other-Category Mimics

— Asynchronous limb movements, pelvic thrusting, side-to-side head shaking, eyes closed (epileptic seizures usually have eyes open), preserved awareness during "generalized" event, prolonged duration with normal vitals, no postictal confusion, no Todd paralysis

— Normal lactate and prolactin (prolactin doubles within 20 min of true generalized seizure but is nonspecific)

— Video EEG is gold standard

— Don't intubate or load with anesthetics — but treat empirically as SE if uncertain

— Brief tonic-clonic jerks (5–15 sec), no postictal confusion, pallor preceding event, rapid recovery — vasovagal trigger

— Workup: ECG, orthostatics, echo if structural cause suspected

— Focal deficits without rhythmic movements; CT distinguishes

— Postictal Todd paralysis can mimic stroke — typically resolves within 24h

— Always check basic metabolics; correct cause as primary treatment

— Fever, meningismus, headache, immunocompromise → empiric ceftriaxone + vancomycin + acyclovir + dexamethasone while awaiting LP

— Cocaine, methamphetamine, bupropion, tramadol, TCAs, isoniazid → toxidromes

— Alcohol withdrawal seizures (6–48h after last drink) — benzodiazepines, thiamine

— Benzodiazepine withdrawal — restart benzo, slow taper

— Not seizure activity; signals impending herniation — emergent neurosurgical evaluation, hyperventilation, mannitol/hypertonic saline

Step 3 management: When PNES is strongly suspected but you cannot confirm in real time, err on the side of treating as SE — give benzodiazepine but avoid escalation to anesthetic infusion without EEG confirmation. Document carefully.

Psychogenic nonepileptic seizures (PNES) / functional seizures:

Syncope with convulsive jerks (convulsive syncope):

Stroke and intracerebral hemorrhage:

Hypoglycemia, hyponatremia, hypocalcemia, hypomagnesemia, uremia, hepatic encephalopathy:

CNS infection (meningitis, encephalitis, abscess):

Drug intoxication/withdrawal:

Decerebrate/decorticate posturing from herniation:

Movement disorders: dystonic storm, serotonin syndrome (clonus, hyperthermia, autonomic instability), neuroleptic malignant syndrome — clue from medication history

Secondary Prevention, Discharge Medications, and Long-Term Plan

— Continue the second-line AED used acutely (typically levetiracetam 1000–1500 mg PO BID) as initial maintenance

— Tailor based on etiology, comorbidities, pregnancy plans, and seizure type:

— Focal epilepsy: lamotrigine, levetiracetam, lacosamide, oxcarbazepine

— Generalized: levetiracetam, valproate (not in women of childbearing potential), lamotrigine

— Post-stroke: levetiracetam preferred

— Avoid abrupt discontinuation; if switching agents, overlap and taper

— Known epileptics: most common cause is AED nonadherence — review barriers (cost, side effects, complex regimens); simplify, consider once-daily ER formulations

— Treat underlying stroke, infection, tumor, metabolic abnormality

— Alcohol use disorder: naltrexone or acamprosate, AA referral, social work

— Sleep deprivation, missed meals — counsel

— State-specific (3–12 months seizure-free typical); patient must be informed in writing

— Some states (CA, NV, OR, NJ, PA, DE) require physician reporting of seizure to DMV

— Document the conversation in the chart

— Avoid heights, swimming alone, driving, operating heavy machinery, climbing ladders until seizure-free

— Showers preferred over baths (drowning risk)

— SUDEP (sudden unexpected death in epilepsy) discussion — rare but real, ↓ by good seizure control

— Prescribe intranasal midazolam or rectal diazepam for cluster seizures at home; train family in use and when to call 911 (>5 min seizure)

Step 3 management: On discharge after SE, set up neurology follow-up within 1–2 weeks, check AED level at follow-up, and provide a written seizure action plan including rescue medication. This bundle is repeatedly tested.

Maintenance AED selection (after acute SE controlled):

Address precipitating factor (essential for prevention):

Driving restrictions:

Safety counseling:

Rescue plan:

Vaccinations: pneumococcal, influenza (some AEDs immunosuppressive long-term, e.g., valproate rarely)

Follow-Up, Monitoring, and Rehabilitation

— Neurology within 1–2 weeks of discharge; sooner if AED changes are complex

— Primary care within 1 week to coordinate care, review medications, screen for depression/anxiety (40% prevalence in epilepsy)

— Outpatient EEG within 4–6 weeks if not done inpatient

— MRI brain within 4–6 weeks if not completed inpatient and etiology unclear

— Phenytoin: trough level (target total 10–20, free 1–2 mcg/mL); CBC, LFTs at baseline and yearly; watch gingival hyperplasia, hirsutism, osteopenia (DEXA q2–3 years on chronic use), Stevens-Johnson (HLA-B*1502 in Asian patients — screen before initiation)

— Valproate: trough 50–100 mcg/mL; CBC, LFTs, ammonia, lipase at baseline, 1, 3, 6 months, then q6–12 months; pregnancy testing in women

— Levetiracetam: levels not routinely needed; monitor for behavioral changes, depression, suicidal ideation; renal function annually

— Carbamazepine: CBC (aplastic anemia, neutropenia), Na (SIADH), LFTs; HLA-B*1502 screening in Asian patients

— Lamotrigine: slow titration to prevent rash/SJS/TEN; valproate doubles lamotrigine levels (halve dose)

— Lacosamide: PR interval on ECG at baseline if cardiac history

— Neuropsychological evaluation if persistent deficits 3–6 months post-SE

— Speech, OT, PT as indicated

— Vocational rehabilitation if work impaired

— Mental health: screen for depression (PHQ-9), anxiety, suicidal ideation (some AEDs ↑ risk)

— Support groups, Epilepsy Foundation resources

Board pearl: Lamotrigine titration must be slow — too-rapid escalation, especially with concurrent valproate, causes Stevens-Johnson syndrome / TEN. Step 3 may show a rash with mucosal involvement on day 14 after starting; stop drug, admit, supportive care.

Outpatient follow-up cadence:

AED monitoring parameters:

Cognitive and psychosocial rehab:

Bone health: Enzyme-inducing AEDs (phenytoin, carbamazepine, phenobarbital) ↓ vitamin D and bone density — supplement calcium 1200 mg/day + vitamin D 1000–2000 IU/day; DEXA q2–3 years.

Ethical, Legal, and Patient Safety Considerations

— Emergency exception applies — implied consent for life-saving treatment (benzodiazepines, intubation, anesthetic infusion)

— Once stabilized, obtain consent for non-emergent procedures (LP, lines, MRI with contrast)

— If patient lacks capacity post-SE, identify surrogate per state hierarchy (spouse → adult child → parent → sibling)

— Document discussion of driving restrictions in chart — failure to counsel is a known liability source

— Six US states have mandatory physician reporting to DMV for seizures (CA, NV, OR, NJ, PA, DE); most others encourage voluntary reporting

— Patient counseling itself does not require consent, but reporting to DMV may involve breaching confidentiality — handle per state law

— Medication reconciliation at admission, transfer, and discharge — AED omission is a Joint Commission–tracked never event in many systems

— Provide written discharge instructions in patient's preferred language; teach-back to confirm understanding

— Communicate directly with outpatient neurologist or PCP, not just by sending records

— Super-refractory SE >7 days with poor prognostic features (anoxic brain injury, age, comorbidities) raises goals-of-care discussions with family

— Use multidisciplinary family meeting; involve palliative care early; honor advance directives

— Withdrawal of anesthetic with comfort-focused care if family elects

— Seizure precautions: padded side rails, suction at bedside, bed in low position, no oral thermometer or restraints

— Fall risk assessment and prevention bundles

— Restraint use only with documented behavioral/safety justification — reassess every 4h

— Encourage enrollment in the North American AED Pregnancy Registry for any patient continuing AEDs through pregnancy — contributes to evidence base

— Typically restricted 3–6 months (state-specific), even if EEG normal, since recurrence risk is ~30–40% within 2 years

Step 3 management: When in doubt about a patient's capacity post-SE (subtle NCSE, residual encephalopathy), delay non-urgent decisions and obtain formal capacity assessment rather than relying on a single examination — protects both patient and clinician.

Informed consent in the acutely seizing patient:

Driving and mandatory reporting:

Transitions of care (high-risk for AED errors):

End-of-life and refractory SE:

Safety in hospital:

Pregnancy registries:

Driving after first-ever seizure:

High-Yield Associations and Rapid-Fire Facts

CCS pearl: Always order CK, thiamine, glucose, pregnancy test, and tox screen alongside benzodiazepine on the very first CCS screen for any new seizure — these orders score points and reflect real practice.

The 5-minute rule: Convulsive activity ≥5 min = treat as SE. Don't wait.

First drug, full dose: Lorazepam 4 mg IV (or 0.1 mg/kg) — underdosing causes refractory SE.

IM midazolam = IV lorazepam in efficacy (RAMPART trial) when IV access delayed.

ESETT trial: Levetiracetam, fosphenytoin, valproate roughly equivalent (~45% efficacy) for second-line. Choose based on contraindications.

Isoniazid seizure: Give pyridoxine (B6) 5 g IV — refractory to benzos alone.

Eclampsia: Magnesium sulfate is first-line, NOT benzodiazepines. Antidote = calcium gluconate.

Alcohol withdrawal seizures: Benzodiazepines + thiamine; avoid phenytoin (doesn't work for ethanol withdrawal seizures).

NCSE in coma: Any unexplained coma after CSE or in critical illness → continuous EEG.

Pediatric refractory neonatal SE: Try pyridoxine for pyridoxine-dependent epilepsy.

Pregnancy AEDs: Best safety = levetiracetam, lamotrigine. Worst = valproate (neural tube defects, ↓ IQ).

Free phenytoin in renal failure or hypoalbuminemia — total level is misleading.

Propofol infusion syndrome: metabolic acidosis + rhabdo + cardiac failure; limit >80 mcg/kg/min for prolonged use.

NORSE: new-onset refractory SE in previously healthy adult → autoimmune encephalitis (anti-NMDA, ovarian teratoma in young women) workup + immunotherapy.

Phenytoin compatibility: normal saline only (precipitates in D5W); through a filter; ≤50 mg/min to avoid hypotension/arrhythmia.

Phenytoin extravasation: purple glove syndrome — limb ischemia.

Lactate post-seizure: elevated, but clears within 60–90 minutes; persistent lactate → NCSE or sepsis.

Tongue bite location: lateral = epileptic; tip = nonspecific.

SUDEP: rare but real; better seizure control reduces risk.

Generalized epilepsies: Avoid carbamazepine, phenytoin, oxcarbazepine — may worsen absence/myoclonic seizures.

Lamotrigine + valproate: halve lamotrigine dose; titrate slowly to prevent SJS.

AED nonadherence = #1 cause of breakthrough seizures in known epileptics.

Board Question Stem Patterns

Board pearl: When a stem describes "continued altered mental status without movement" after a seizure stops, the answer is almost always continuous EEG to evaluate for nonconvulsive SE.

Stem 1 — Classic CSE: A 32-year-old man with epilepsy is brought in seizing for 8 minutes. Vitals 160/95, HR 130, SpO₂ 92%. Next step: IV lorazepam 4 mg. Then: if persists at 5 min, repeat; at 10–20 min, load levetiracetam 60 mg/kg IV.

Stem 2 — RSE → ICU: Same patient continues seizing after 2 doses of lorazepam and levetiracetam. Next: intubate, transfer ICU, midazolam infusion, continuous EEG.

Stem 3 — INH overdose: Tuberculosis patient brought in with refractory seizures after suicide attempt; benzodiazepines minimally effective. Answer: pyridoxine 5 g IV.

Stem 4 — Eclampsia: 28 weeks pregnant, BP 180/110, seizing. First-line: magnesium sulfate IV, not benzodiazepine. Then: labetalol for BP, delivery planning.

Stem 5 — NCSE: Patient with prior CSE remains comatose 1 hour after seizure stopped. Next: continuous EEG (will show electrographic seizures).

Stem 6 — Alcohol withdrawal: Day 2 of hospitalization, tremulous patient has generalized seizure. Treatment: benzodiazepines (CIWA protocol), thiamine 100 mg IV before glucose, folate.

Stem 7 — NORSE: Previously healthy 24-year-old woman with psychiatric prodrome, refractory SE. Workup: anti-NMDA antibody, pelvic imaging for ovarian teratoma. Treatment: IV methylprednisolone, IVIG, tumor resection.

Stem 8 — Hypoglycemic seizure: Diabetic on insulin found seizing, glucose 32. Treatment: thiamine 100 mg IV then D50 50 mL IV — no AED loading needed if glucose correction resolves it.

Stem 9 — Postpartum new seizure: 5 days postpartum, sudden seizure + headache. Differential: eclampsia, cerebral venous sinus thrombosis (get MRV), PRES, pituitary apoplexy.

Stem 10 — Driving counseling: Patient asks when she can drive after first SE. Answer: state-specific, typically 3–6 months seizure-free; document discussion; in mandatory-reporting states, file with DMV.

Stem 11 — Free phenytoin: ESRD patient on phenytoin with low albumin, total level 6 (low) but ataxic and somnolent. Answer: check free phenytoin — likely toxic.

Stem 12 — Propofol infusion syndrome: ICU SE patient on prolonged high-dose propofol develops metabolic acidosis, ↑CK, ↑triglycerides. Answer: stop propofol, switch to midazolam or pentobarbital.

One-Line Recap

Status epilepticus is a time-critical neurologic emergency where every minute of delay in delivering full-dose IV (or IM) benzodiazepines followed by a second-line AED (levetiracetam, fosphenytoin, or valproate) within 20 minutes — and escalation to ICU-level anesthetic infusion with continuous EEG by 40–60 minutes — directly determines neuronal survival and long-term outcome.

CCS pearl: On every CCS seizure case, the first screen should read: "IV access, O₂, monitor, fingerstick glucose, lorazepam 4 mg IV, thiamine, labs (CBC/BMP/LFTs/Ca/Mg/CK/tox/AED levels/β-hCG), ECG" — all simultaneous. Sequential ordering loses time and points.

Time wins: 5-minute operational threshold → lorazepam 4 mg IV (or IM midazolam 10 mg) → repeat at 5 min → levetiracetam 60 mg/kg IV at 20 min → anesthetic infusion + intubation + cEEG at 40–60 min.

Never miss the mimics: check fingerstick glucose immediately; suspect eclampsia in pregnancy (magnesium, not benzo); pyridoxine for INH overdose; alcohol withdrawal needs benzo + thiamine; new-onset refractory SE in young adult → autoimmune encephalitis workup.

Don't stop at motor cessation: persistent altered mental status after seizures stop = nonconvulsive SE until continuous EEG proves otherwise; up to 30% of comatose ICU patients have undiagnosed electrographic seizures.

Discharge bundle: address etiology, optimize maintenance AED (levetiracetam first-line for most), counsel on driving restrictions and home rescue medication, arrange neurology follow-up within 1–2 weeks, screen for depression and AED adherence, and document mandatory reporting where applicable.